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Innate and adaptive immune responses against Staphylococcus aureus skin infections

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Abstract

Staphylococcus aureus is an important human pathogen that is responsible for the vast majority of bacterial skin and soft tissue infections in humans. S. aureus can also become more invasive and cause life-threatening infections such as bacteremia, pneumonia, abscesses of various organs, meningitis, osteomyelitis, endocarditis, and sepsis. These infections represent a major public health threat due to the enormous numbers of these infections and the widespread emergence of methicillin-resistant S. aureus (MRSA) strains. MSRA is endemic in hospitals worldwide and is rapidly spreading throughout the normal human population in the community. The increasing frequency of MRSA infections has complicated treatment as these strains are more virulent and are increasingly becoming resistant to multiple different classes of antibiotics. The important role of the immune response against S. aureus infections cannot be overemphasized as humans with certain genetic and acquired immunodeficiency disorders are at an increased risk for infection. Understanding the cutaneous immune responses against S. aureus is essential as most of these infections occur or originate from a site of infection or colonization of the skin and mucosa. This review will summarize the innate immune responses against S. aureus skin infections, including antimicrobial peptides that have direct antimicrobial activity against S. aureus as well as pattern recognition receptors and proinflammatory cytokines that promote neutrophil abscess formation in the skin, which is required for bacterial clearance. Finally, we will discuss the recent discoveries involving IL-17-mediated responses, which provide a key link between cutaneous innate and adaptive immune responses against S. aureus skin infections.

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References

  1. McCaig LF, McDonald LC, Mandal S, Jernigan DB (2006) Staphylococcus aureus-associated skin and soft tissue infections in ambulatory care. Emerg Infect Dis 12:1715–1723

    Article  PubMed  Google Scholar 

  2. Moran GJ, Krishnadasan A, Gorwitz RJ, Fosheim GE, McDougal LK, Carey RB, Talan DA (2006) Methicillin-resistant S. aureus infections among patients in the emergency department. N Engl J Med 355:666–674

    Article  PubMed  CAS  Google Scholar 

  3. Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, Harrison LH, Lynfield R, Dumyati G, Townes JM, Craig AS, Zell ER, Fosheim GE, McDougal LK, Carey RB, Fridkin SK (2007) Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA 298:1763–1771

    Article  PubMed  CAS  Google Scholar 

  4. Daum RS (2007) Clinical practice. Skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus. N Engl J Med 357:380–390

    Article  PubMed  CAS  Google Scholar 

  5. Deleo FR, Otto M, Kreiswirth BN, Chambers HF (2010) Community-associated methicillin-resistant Staphylococcus aureus. Lancet 375:1557–1568

    Article  PubMed  Google Scholar 

  6. Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, Rybak J, Talan DA, Chambers HF (2011) Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 52:e18–e55

    Article  PubMed  Google Scholar 

  7. Gorwitz RJ, Kruszon-Moran D, McAllister SK, McQuillan G, McDougal LK, Fosheim GE, Jensen BJ, Killgore G, Tenover FC, Kuehnert MJ (2008) Changes in the prevalence of nasal colonization with Staphylococcus aureus in the United States, 2001–2004. J Infect Dis 197:1226–1234

    Article  PubMed  Google Scholar 

  8. Hidron AI, Kourbatova EV, Halvosa JS, Terrell BJ, McDougal LK, Tenover FC, Blumberg HM, King MD (2005) Risk factors for colonization with methicillin-resistant Staphylococcus aureus (MRSA) in patients admitted to an urban hospital: emergence of community-associated MRSA nasal carriage. Clin Infect Dis 41:159–166

    Article  PubMed  Google Scholar 

  9. Miller LS, Cho JS (2011) Immunity against Staphylococcus aureus cutaneous infections. Nat Rev Immunol 11:505–518

    Article  PubMed  CAS  Google Scholar 

  10. Kupper TS, Fuhlbrigge RC (2004) Immune surveillance in the skin: mechanisms and clinical consequences. Nat Rev Immunol 4:211–222

    Article  PubMed  CAS  Google Scholar 

  11. Nestle FO, Di MP, Qin JZ, Nickoloff BJ (2009) Skin immune sentinels in health and disease. Nat Rev Immunol 9:679–691

    PubMed  CAS  Google Scholar 

  12. Takeuchi O, Akira S (2010) Pattern recognition receptors and inflammation. Cell 140:805–820

    Article  PubMed  CAS  Google Scholar 

  13. Girardi M (2007) Cutaneous perspectives on adaptive immunity. Clin Rev Allergy Immunol 33:4–14

    Article  PubMed  CAS  Google Scholar 

  14. Simanski M, Dressel S, Glaser R, Harder J (2010) RNase 7 protects healthy skin from Staphylococcus aureus colonization. J Invest Dermatol 130:2836–2838

    Article  PubMed  CAS  Google Scholar 

  15. Braff MH, Zaiou M, Fierer J, Nizet V, Gallo RL (2005) Keratinocyte production of cathelicidin provides direct activity against bacterial skin pathogens. Infect Immun 73:6771–6781

    Article  PubMed  CAS  Google Scholar 

  16. Kisich KO, Howell MD, Boguniewicz M, Heizer HR, Watson NU, Leung DY (2007) The constitutive capacity of human keratinocytes to kill Staphylococcus aureus is dependent on beta-defensin 3. J Invest Dermatol 127:2368–2380

    Article  PubMed  CAS  Google Scholar 

  17. Harder J, Bartels J, Christophers E, Schroder JM (2001) Isolation and characterization of human beta-defensin-3, a novel human inducible peptide antibiotic. J Biol Chem 276:5707–5713

    Article  PubMed  CAS  Google Scholar 

  18. Harder J, Bartels J, Christophers E, Schroder JM (1997) A peptide antibiotic from human skin. Nature 387:861

    Article  PubMed  CAS  Google Scholar 

  19. Miller LS (2008) Toll-like receptors in skin. Adv Dermatol 24:71–87

    Article  PubMed  Google Scholar 

  20. Lai Y, Cogen AL, Radek KA, Park HJ, Macleod DT, Leichtle A, Ryan AF, Di NA, Gallo RL (2010) Activation of TLR2 by a small molecule produced by Staphylococcus epidermidis increases antimicrobial defense against bacterial skin infections. J Invest Dermatol 130:2211–2221

    Article  PubMed  CAS  Google Scholar 

  21. Wanke I, Steffen H, Christ C, Krismer B, Gotz F, Peschel A, Schaller M, Schittek B (2011) Skin commensals amplify the innate immune response to pathogens by activation of distinct signaling pathways. J Invest Dermatol 131:382–390

    Article  PubMed  CAS  Google Scholar 

  22. Elston DM (2007) Community-acquired methicillin-resistant Staphylococcus aureus. J Am Acad Dermatol 56:1–16

    Article  PubMed  Google Scholar 

  23. Miller LS, O'Connell RM, Gutierrez MA, Pietras EM, Shahangian A, Gross CE, Thirumala A, Cheung AL, Cheng G, Modlin RL (2006) MyD88 mediates neutrophil recruitment initiated by IL-1R but not TLR2 activation in immunity against Staphylococcus aureus. Immunity 24:79–91

    Article  PubMed  CAS  Google Scholar 

  24. Molne L, Verdrengh M, Tarkowski A (2000) Role of neutrophil leukocytes in cutaneous infection caused by Staphylococcus aureus. Infect Immun 68:6162–6167

    Article  PubMed  CAS  Google Scholar 

  25. Verdrengh M, Tarkowski A (1997) Role of neutrophils in experimental septicemia and septic arthritis induced by Staphylococcus aureus. Infect Immun 65:2517–2521

    PubMed  CAS  Google Scholar 

  26. Segal AW (2005) How neutrophils kill microbes. Annu Rev Immunol 23:197–223

    Article  PubMed  CAS  Google Scholar 

  27. Bouma G, Ancliff PJ, Thrasher AJ, Burns SO (2010) Recent advances in the understanding of genetic defects of neutrophil number and function. Br J Haematol 151:312–326

    Article  PubMed  CAS  Google Scholar 

  28. Lakshman R, Finn A (2001) Neutrophil disorders and their management. J Clin Pathol 54:7–19

    Article  PubMed  CAS  Google Scholar 

  29. Andrews T, Sullivan KE (2003) Infections in patients with inherited defects in phagocytic function. Clin Microbiol Rev 16:597–621

    Article  PubMed  CAS  Google Scholar 

  30. Gonzalez-Barca E, Carratala J, Mykietiuk A, Fernandez-Sevilla A, Gudiol F (2001) Predisposing factors and outcome of Staphylococcus aureus bacteremia in neutropenic patients with cancer. Eur J Clin Microbiol Infect Dis 20:117–119

    Article  PubMed  CAS  Google Scholar 

  31. Alba-Loureiro TC, Munhoz CD, Martins JO, Cerchiaro GA, Scavone C, Curi R, Sannomiya P (2007) Neutrophil function and metabolism in individuals with diabetes mellitus. Braz J Med Biol Res 40:1037–1044

    Article  PubMed  CAS  Google Scholar 

  32. Chonchol M (2006) Neutrophil dysfunction and infection risk in end-stage renal disease. Semin Dial 19:291–296

    Article  PubMed  Google Scholar 

  33. Ku CL, von BH, Picard C, Zhang SY, Chang HH, Yang K, Chrabieh M, Issekutz AC, Cunningham CK, Gallin J, Holland SM, Roifman C, Ehl S, Smart J, Tang M, Barrat FJ, Levy O, McDonald D, Day-Good NK, Miller R, Takada H, Hara T, Al-Hajjar S, Al-Ghonaium A, Speert D, Sanlaville D, Li X, Geissmann F, Vivier E, Marodi L, Garty BZ, Chapel H, Rodriguez-Gallego C, Bossuyt X, Abel L, Puel A, Casanova JL (2007) Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity. J Exp Med 204:2407–2422

    Article  PubMed  CAS  Google Scholar 

  34. Picard C, Puel A, Bonnet M, Ku CL, Bustamante J, Yang K, Soudais C, Dupuis S, Feinberg J, Fieschi C, Elbim C, Hitchcock R, Lammas D, Davies G, Al-Ghonaium A, Al-Rayes H, Al-Jumaah S, Al-Hajjar S, Al-Mohsen IZ, Frayha HH, Rucker R, Hawn TR, Aderem A, Tufenkeji H, Haraguchi S, Day NK, Good RA, Gougerot-Pocidalo MA, Ozinsky A, Casanova JL (2003) Pyogenic bacterial infections in humans with IRAK-4 deficiency. Science 299:2076–2079

    Article  PubMed  CAS  Google Scholar 

  35. von Bernuth H, Picard C, Jin Z, Pankla R, Xiao H, Ku CL, Chrabieh M, Mustapha IB, Ghandil P, Camcioglu Y, Vasconcelos J, Sirvent N, Guedes M, Vitor AB, Herrero-Mata MJ, Arostegui JI, Rodrigo C, Alsina L, Ruiz-Ortiz E, Juan M, Fortuny C, Yague J, Anton J, Pascal M, Chang HH, Janniere L, Rose Y, Garty BZ, Chapel H, Issekutz A, Marodi L, Rodriguez-Gallego C, Banchereau J, Abel L, Li X, Chaussabel D, Puel A, Casanova JL (2008) Pyogenic bacterial infections in humans with MyD88 deficiency. Science 321:691–696

    Article  CAS  Google Scholar 

  36. Picard C, von BH, Ghandil P, Chrabieh M, Levy O, Arkwright PD, McDonald D, Geha RS, Takada H, Krause JC, Creech CB, Ku CL, Ehl S, Marodi L, Al-Muhsen S, Al-Hajjar S, Al-Ghonaium A, Day-Good NK, Holland SM, Gallin JI, Chapel H, Speert DP, Rodriguez-Gallego C, Colino E, Garty BZ, Roifman C, Hara T, Yoshikawa H, Nonoyama S, Domachowske J, Issekutz AC, Tang M, Smart J, Zitnik SE, Hoarau C, Kumararatne DS, Thrasher AJ, Davies EG, Bethune C, Sirvent N, de RD, Camcioglu Y, Vasconcelos J, Guedes M, Vitor AB, Rodrigo C, Almazan F, Mendez M, Arostegui JI, Alsina L, Fortuny C, Reichenbach J, Verbsky JW, Bossuyt X, Doffinger R, Abel L, Puel A, Casanova JL (2010) Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency. Med (Baltimore) 89:403–425

    Article  CAS  Google Scholar 

  37. Guttman-Yassky E, Lowes MA, Fuentes-Duculan J, Zaba LC, Cardinale I, Nograles KE, Khatcherian A, Novitskaya I, Carucci JA, Bergman R, Krueger JG (2008) Low expression of the IL-23/Th17 pathway in atopic dermatitis compared to psoriasis. J Immunol 181:7420–7427

    PubMed  CAS  Google Scholar 

  38. Prendergast A, Prado JG, Kang YH, Chen F, Riddell LA, Luzzi G, Goulder P, Klenerman P (2010) HIV-1 infection is characterized by profound depletion of CD161+ Th17 cells and gradual decline in regulatory T cells. AIDS 24:491–502

    Article  PubMed  Google Scholar 

  39. Al KS, Keles S, Garcia-Lloret M, Karakoc-Aydiner E, Reisli I, Artac H, Camcioglu Y, Cokugras H, Somer A, Kutukculer N, Yilmaz M, Ikinciogullari A, Yegin O, Yuksek M, Genel F, Kucukosmanoglu E, Baki A, Bahceciler NN, Rambhatla A, Nickerson DW, McGhee S, Barlan IB, Chatila T (2009) Defects along the T(H)17 differentiation pathway underlie genetically distinct forms of the hyper IgE syndrome. J Allergy Clin Immunol 124(342–8):348

    Google Scholar 

  40. Renner ED, Rylaarsdam S, nover-Sombke S, Rack AL, Reichenbach J, Carey JC, Zhu Q, Jansson AF, Barboza J, Schimke LF, Leppert MF, Getz MM, Seger RA, Hill HR, Belohradsky BH, Torgerson TR, Ochs HD (2008) Novel signal transducer and activator of transcription 3 (STAT3) mutations, reduced T(H)17 cell numbers, and variably defective STAT3 phosphorylation in hyper-IgE syndrome. J Allergy Clin Immunol 122:181–187

    Article  PubMed  CAS  Google Scholar 

  41. Ma CS, Chew GY, Simpson N, Priyadarshi A, Wong M, Grimbacher B, Fulcher DA, Tangye SG, Cook MC (2008) Deficiency of Th17 cells in hyper IgE syndrome due to mutations in STAT3. J Exp Med 205:1551–1557

    Article  PubMed  CAS  Google Scholar 

  42. Milner JD, Brenchley JM, Laurence A, Freeman AF, Hill BJ, Elias KM, Kanno Y, Spalding C, Elloumi HZ, Paulson ML, Davis J, Hsu A, Asher AI, O'Shea J, Holland SM, Paul WE, Douek DC (2008) Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature 452:773–776

    Article  PubMed  CAS  Google Scholar 

  43. Kim MH, Granick JL, Kwok C, Walker NJ, Borjesson DL, Curry FR, Miller LS, Simon SI (2011) Neutrophil survival and c-kit+-progenitor proliferation in Staphylococcus aureus-infected skin wounds promote resolution. Blood 117:3343–3352

    Article  PubMed  CAS  Google Scholar 

  44. Fournier B, Philpott DJ (2005) Recognition of Staphylococcus aureus by the innate immune system. Clin Microbiol Rev 18:521–540

    Article  PubMed  CAS  Google Scholar 

  45. Ley K, Laudanna C, Cybulsky MI, Nourshargh S (2007) Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol 7:678–689

    Article  PubMed  CAS  Google Scholar 

  46. Corbin BD, Seeley EH, Raab A, Feldmann J, Miller MR, Torres VJ, Anderson KL, Dattilo BM, Dunman PM, Gerads R, Caprioli RM, Nacken W, Chazin WJ, Skaar EP (2008) Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319:962–965

    Article  PubMed  CAS  Google Scholar 

  47. Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A (2004) Neutrophil extracellular traps kill bacteria. Science 303:1532–1535

    Article  PubMed  CAS  Google Scholar 

  48. Pilsczek FH, Salina D, Poon KK, Fahey C, Yipp BG, Sibley CD, Robbins SM, Green FH, Surette MG, Sugai M, Bowden MG, Hussain M, Zhang K, Kubes P (2010) A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus. J Immunol 185:7413–7425

    Article  PubMed  CAS  Google Scholar 

  49. Urban CF, Lourido S, Zychlinsky A (2006) How do microbes evade neutrophil killing? Cell Microbiol 8:1687–1696

    Article  PubMed  CAS  Google Scholar 

  50. Postma B, Poppelier MJ, van Galen JC, Prossnitz ER, van Strijp JA, de Haas CJ, van Kessel KP (2004) Chemotaxis inhibitory protein of Staphylococcus aureus binds specifically to the C5a and formylated peptide receptor. J Immunol 172:6994–7001

    PubMed  CAS  Google Scholar 

  51. Athanasopoulos AN, Economopoulou M, Orlova VV, Sobke A, Schneider D, Weber H, Augustin HG, Eming SA, Schubert U, Linn T, Nawroth PP, Hussain M, Hammes HP, Herrmann M, Preissner KT, Chavakis T (2006) The extracellular adherence protein (Eap) of Staphylococcus aureus inhibits wound healing by interfering with host defense and repair mechanisms. Blood 107:2720–2727

    Article  PubMed  CAS  Google Scholar 

  52. Foster TJ (2005) Immune evasion by staphylococci. Nat Rev Microbiol 3:948–958

    Article  PubMed  CAS  Google Scholar 

  53. Rooijakkers SH, van Kessel KP, van Strijp JA (2005) Staphylococcal innate immune evasion. Trends Microbiol 13:596–601

    Article  PubMed  CAS  Google Scholar 

  54. Wang R, Braughton KR, Kretschmer D, Bach TH, Queck SY, Li M, Kennedy AD, Dorward DW, Klebanoff SJ, Peschel A, Deleo FR, Otto M (2007) Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA. Nat Med 13:1510–1514

    Article  PubMed  CAS  Google Scholar 

  55. Otto M (2010) Basis of virulence in community-associated methicillin-resistant Staphylococcus aureus. Annu Rev Microbiol 64:143–162

    Article  PubMed  CAS  Google Scholar 

  56. Liu GY, Essex A, Buchanan JT, Datta V, Hoffman HM, Bastian JF, Fierer J, Nizet V (2005) Staphylococcus aureus golden pigment impairs neutrophil killing and promotes virulence through its antioxidant activity. J Exp Med 202:209–215

    Article  PubMed  CAS  Google Scholar 

  57. Karavolos MH, Horsburgh MJ, Ingham E, Foster SJ (2003) Role and regulation of the superoxide dismutases of Staphylococcus aureus. Microbiology 149:2749–2758

    Article  PubMed  CAS  Google Scholar 

  58. McLoughlin RM, Lee JC, Kasper DL, Tzianabos AO (2008) IFN-gamma regulated chemokine production determines the outcome of Staphylococcus aureus infection. J Immunol 181:1323–1332

    PubMed  CAS  Google Scholar 

  59. Palazzolo-Ballance AM, Reniere ML, Braughton KR, Sturdevant DE, Otto M, Kreiswirth BN, Skaar EP, Deleo FR (2008) Neutrophil microbicides induce a pathogen survival response in community-associated methicillin-resistant Staphylococcus aureus. J Immunol 180:500–509

    PubMed  CAS  Google Scholar 

  60. Schauber J, Gallo RL (2009) Antimicrobial peptides and the skin immune defense system. J Allergy Clin Immunol 124:R13–R18

    Article  PubMed  CAS  Google Scholar 

  61. Otto M (2010) Staphylococcus colonization of the skin and antimicrobial peptides. Expert Rev Dermatol 5:183–195

    Article  PubMed  CAS  Google Scholar 

  62. Cho JS, Xuan C, Miller LS (2010) Lucky number seven: RNase 7 can prevent Staphylococcus aureus skin colonization. J Invest Dermatol 130:2703–2706

    Article  PubMed  CAS  Google Scholar 

  63. Miller LS, Sorensen OE, Liu PT, Jalian HR, Eshtiaghpour D, Behmanesh BE, Chung W, Starner TD, Kim J, Sieling PA, Ganz T, Modlin RL (2005) TGF-a regulates TLR expression and function on epidermal keratinocytes. J Immunol 174:6137–6143

    PubMed  CAS  Google Scholar 

  64. Sorensen OE, Thapa DR, Roupe KM, Valore EV, Sjobring U, Roberts AA, Schmidtchen A, Ganz T (2006) Injury-induced innate immune response in human skin mediated by transactivation of the epidermal growth factor receptor. J Clin Invest 116:1878–1885

    Article  PubMed  CAS  Google Scholar 

  65. Lehrer RI (2007) Multispecific myeloid defensins. Curr Opin Hematol 14:16–21

    Article  PubMed  CAS  Google Scholar 

  66. Ericksen B, Wu Z, Lu W, Lehrer RI (2005) Antibacterial activity and specificity of the six human a-defensins. Antimicrob Agents Chemother 49:269–275

    Article  PubMed  CAS  Google Scholar 

  67. Garcia JR, Krause A, Schulz S, Rodriguez-Jimenez FJ, Kluver E, Adermann K, Forssmann U, Frimpong-Boateng A, Bals R, Forssmann WG (2001) Human b-defensin 4: a novel inducible peptide with a specific salt-sensitive spectrum of antimicrobial activity. FASEB J 15:1819–1821

    PubMed  CAS  Google Scholar 

  68. Jann NJ, Schmaler M, Kristian SA, Radek KA, Gallo RL, Nizet V, Peschel A, Landmann R (2009) Neutrophil antimicrobial defense against Staphylococcus aureus is mediated by phagolysosomal but not extracellular trap-associated cathelicidin. J Leukoc Biol 86:1159–1169

    Article  PubMed  CAS  Google Scholar 

  69. Rieg S, Steffen H, Seeber S, Humeny A, Kalbacher H, Dietz K, Garbe C, Schittek B (2005) Deficiency of dermcidin-derived antimicrobial peptides in sweat of patients with atopic dermatitis correlates with an impaired innate defense of human skin in vivo. J Immunol 174:8003–8010

    PubMed  CAS  Google Scholar 

  70. Steffen H, Rieg S, Wiedemann I, Kalbacher H, Deeg M, Sahl HG, Peschel A, Gotz F, Garbe C, Schittek B (2006) Naturally processed dermcidin-derived peptides do not permeabilize bacterial membranes and kill microorganisms irrespective of their charge. Antimicrob Agents Chemother 50:2608–2620

    Article  PubMed  CAS  Google Scholar 

  71. Dinulos JG, Mentele L, Fredericks LP, Dale BA, Darmstadt GL (2003) Keratinocyte expression of human beta-defensin 2 following bacterial infection: role in cutaneous host defense. Clin Diagn Lab Immunol 10:161–166

    PubMed  CAS  Google Scholar 

  72. Menzies BE, Kenoyer A (2006) Signal transduction and nuclear responses in Staphylococcus aureus-induced expression of human beta-defensin 3 in skin keratinocytes. Infect Immun 74:6847–6854

    Article  PubMed  CAS  Google Scholar 

  73. Sayama K, Komatsuzawa H, Yamasaki K, Shirakata Y, Hanakawa Y, Ouhara K, Tokumaru S, Dai X, Tohyama M, Ten DP, Sugai M, Ichijo H, Hashimoto K (2005) New mechanisms of skin innate immunity: ASK1-mediated keratinocyte differentiation regulates the expression of beta-defensins, LL37, and TLR2. Eur J Immunol 35:1886–1895

    Article  PubMed  CAS  Google Scholar 

  74. Sumikawa Y, Asada H, Hoshino K, Azukizawa H, Katayama I, Akira S, Itami S (2006) Induction of beta-defensin 3 in keratinocytes stimulated by bacterial lipopeptides through Toll-like receptor 2. Microbes Infect 8:1513–1521

    Article  PubMed  CAS  Google Scholar 

  75. Zanger P, Holzer J, Schleucher R, Scherbaum H, Schittek B, Gabrysch S (2010) Severity of Staphylococcus aureus infection of the skin is associated with inducibility of human beta-defensin 3 but not human beta-defensin 2. Infect Immun 78:3112–3117

    Article  PubMed  CAS  Google Scholar 

  76. Miller LS, Modlin RL (2007) Human keratinocyte Toll-like receptors promote distinct immune responses. J Invest Dermatol 127:262–263

    Article  PubMed  CAS  Google Scholar 

  77. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, Ochoa MT, Schauber J, Wu K, Meinken C, Kamen DL, Wagner M, Bals R, Steinmeyer A, Zugel U, Gallo RL, Eisenberg D, Hewison M, Hollis BW, Adams JS, Bloom BR, Modlin RL (2006) Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 311:1770–1773

    Article  PubMed  CAS  Google Scholar 

  78. Schauber J, Dorschner RA, Coda AB, Buchau AS, Liu PT, Kiken D, Helfrich YR, Kang S, Elalieh HZ, Steinmeyer A, Zugel U, Bikle DD, Modlin RL, Gallo RL (2007) Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism. J Clin Invest 117:803–811

    Article  PubMed  CAS  Google Scholar 

  79. Wang TT, Nestel FP, Bourdeau V, Nagai Y, Wang Q, Liao J, Tavera-Mendoza L, Lin R, Hanrahan JW, Mader S, White JH (2004) Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol 173:2909–2912

    PubMed  CAS  Google Scholar 

  80. Ong PY, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T, Gallo RL, Leung DY (2002) Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med 347:1151–1160

    Article  PubMed  CAS  Google Scholar 

  81. Nomura I, Goleva E, Howell MD, Hamid QA, Ong PY, Hall CF, Darst MA, Gao B, Boguniewicz M, Travers JB, Leung DY (2003) Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J Immunol 171:3262–3269

    PubMed  CAS  Google Scholar 

  82. Grigat J, Soruri A, Forssmann U, Riggert J, Zwirner J (2007) Chemoattraction of macrophages, T lymphocytes, and mast cells is evolutionarily conserved within the human alpha-defensin family. J Immunol 179:3958–3965

    PubMed  CAS  Google Scholar 

  83. Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, Anderson M, Schroder JM, Wang JM, Howard OM, Oppenheim JJ (1999) Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 286:525–528

    Article  PubMed  CAS  Google Scholar 

  84. Rohrl J, Yang D, Oppenheim JJ, Hehlgans T (2010) Human beta-defensin 2 and 3 and their mouse orthologs induce chemotaxis through interaction with CCR2. J Immunol 184:6688–6694

    Article  PubMed  CAS  Google Scholar 

  85. De Y, Chen Q, Schmidt AP, Anderson GM, Wang JM, Wooters J, Oppenheim JJ, Chertov O (2000) LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med 192:1069–1074

    Article  Google Scholar 

  86. Tjabringa GS, Ninaber DK, Drijfhout JW, Rabe KF, Hiemstra PS (2006) Human cathelicidin LL-37 is a chemoattractant for eosinophils and neutrophils that acts via formyl-peptide receptors. Int Arch Allergy Immunol 140:103–112

    Article  PubMed  CAS  Google Scholar 

  87. Jin T, Bokarewa M, Foster T, Mitchell J, Higgins J, Tarkowski A (2004) Staphylococcus aureus resists human defensins by production of staphylokinase, a novel bacterial evasion mechanism. J Immunol 172:1169–1176

    PubMed  CAS  Google Scholar 

  88. Clarke SR, Mohamed R, Bian L, Routh AF, Kokai-Kun JF, Mond JJ, Tarkowski A, Foster SJ (2007) The Staphylococcus aureus surface protein IsdA mediates resistance to innate defenses of human skin. Cell Host Microbe 1:199–212

    Article  PubMed  CAS  Google Scholar 

  89. Sieprawska-Lupa M, Mydel P, Krawczyk K, Wojcik K, Puklo M, Lupa B, Suder P, Silberring J, Reed M, Pohl J, Shafer W, McAleese F, Foster T, Travis J, Potempa J (2004) Degradation of human antimicrobial peptide LL-37 by Staphylococcus aureus-derived proteinases. Antimicrob Agents Chemother 48:4673–4679

    Article  PubMed  CAS  Google Scholar 

  90. Peschel A, Jack RW, Otto M, Collins LV, Staubitz P, Nicholson G, Kalbacher H, Nieuwenhuizen WF, Jung G, Tarkowski A, van Kessel KP, van Strijp JA (2001) Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with l-lysine. J Exp Med 193:1067–1076

    Article  PubMed  CAS  Google Scholar 

  91. Ernst CM, Staubitz P, Mishra NN, Yang SJ, Hornig G, Kalbacher H, Bayer AS, Kraus D, Peschel A (2009) The bacterial defensin resistance protein MprF consists of separable domains for lipid lysinylation and antimicrobial peptide repulsion. PLoS Pathog 5:e1000660

    Article  PubMed  CAS  Google Scholar 

  92. Peschel A, Otto M, Jack RW, Kalbacher H, Jung G, Gotz F (1999) Inactivation of the dlt operon in Staphylococcus aureus confers sensitivity to defensins, protegrins, and other antimicrobial peptides. J Biol Chem 274:8405–8410

    Article  PubMed  CAS  Google Scholar 

  93. Lai Y, Villaruz AE, Li M, Cha DJ, Sturdevant DE, Otto M (2007) The human anionic antimicrobial peptide dermcidin induces proteolytic defence mechanisms in staphylococci. Mol Microbiol 63:497–506

    Article  PubMed  CAS  Google Scholar 

  94. Kawai T, Akira S (2011) Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity 34:637–650

    Article  PubMed  CAS  Google Scholar 

  95. Hoebe K, Georgel P, Rutschmann S, Du X, Mudd S, Crozat K, Sovath S, Shamel L, Hartung T, Zahringer U, Beutler B (2005) CD36 is a sensor of diacylglycerides. Nature 433:523–527

    Article  PubMed  CAS  Google Scholar 

  96. Hashimoto M, Tawaratsumida K, Kariya H, Kiyohara A, Suda Y, Krikae F, Kirikae T, Gotz F (2006) Not lipoteichoic acid but lipoproteins appear to be the dominant immunobiologically active compounds in Staphylococcus aureus. J Immunol 177:3162–3169

    PubMed  CAS  Google Scholar 

  97. Takeda K, Takeuchi O, Akira S (2002) Recognition of lipopeptides by Toll-like receptors. J Endotoxin Res 8:459–463

    PubMed  CAS  Google Scholar 

  98. Nilsen NJ, Deininger S, Nonstad U, Skjeldal F, Husebye H, Rodionov D, von AS, Hartung T, Lien E, Bakke O, Espevik T (2008) Cellular trafficking of lipoteichoic acid and Toll-like receptor 2 in relation to signaling: role of CD14 and CD36. J Leukoc Biol 84:280–291

    Article  PubMed  CAS  Google Scholar 

  99. Dziarski R, Gupta D (2005) Staphylococcus aureus peptidoglycan is a toll-like receptor 2 activator: a reevaluation. Infect Immun 73:5212–5216

    Article  PubMed  CAS  Google Scholar 

  100. Muller-Anstett MA, Muller P, Albrecht T, Nega M, Wagener J, Gao Q, Kaesler S, Schaller M, Biedermann T, Gotz F (2010) Staphylococcal peptidoglycan co-localizes with NOD2 and TLR2 and activates innate immune response via both receptors in primary murine keratinocytes. PLoS One 5:e13153

    Article  PubMed  CAS  Google Scholar 

  101. Ahmad-Nejad P, Mrabet-Dahbi S, Breuer K, Klotz M, Werfel T, Herz U, Heeg K, Neumaier M, Renz H (2004) The toll-like receptor 2 R753Q polymorphism defines a subgroup of patients with atopic dermatitis having severe phenotype. J Allergy Clin Immunol 113:565–567

    Article  PubMed  CAS  Google Scholar 

  102. Oh DY, Schumann RR, Hamann L, Neumann K, Worm M, Heine G (2009) Association of the toll-like receptor 2 A-16934T promoter polymorphism with severe atopic dermatitis. Allergy 64:1608–1615

    Article  PubMed  CAS  Google Scholar 

  103. Elinav E, Strowig T, Henao-Mejia J, Flavell RA (2011) Regulation of the antimicrobial response by NLR proteins. Immunity 34:665–679

    Article  PubMed  CAS  Google Scholar 

  104. Garzoni C, Kelley WL (2009) Staphylococcus aureus: new evidence for intracellular persistence. Trends Microbiol 17:59–65

    Article  PubMed  CAS  Google Scholar 

  105. Hruz P, Zinkernagel AS, Jenikova G, Botwin GJ, Hugot JP, Karin M, Nizet V, Eckmann L (2009) NOD2 contributes to cutaneous defense against Staphylococcus aureus through alpha-toxin-dependent innate immune activation. Proc Natl Acad Sci USA 106:12873–12878

    Article  PubMed  CAS  Google Scholar 

  106. Dziarski R, Gupta D (2010) Review: mammalian peptidoglycan recognition proteins (PGRPs) in innate immunity. Innate Immun 16:168–174

    Article  PubMed  CAS  Google Scholar 

  107. Cho JH, Fraser IP, Fukase K, Kusumoto S, Fujimoto Y, Stahl GL, Ezekowitz RA (2005) Human peptidoglycan recognition protein S is an effector of neutrophil-mediated innate immunity. Blood 106:2551–2558

    Article  PubMed  CAS  Google Scholar 

  108. Dziarski R, Platt KA, Gelius E, Steiner H, Gupta D (2003) Defect in neutrophil killing and increased susceptibility to infection with nonpathogenic gram-positive bacteria in peptidoglycan recognition protein-S (PGRP-S)-deficient mice. Blood 102:689–697

    Article  PubMed  CAS  Google Scholar 

  109. Wang ZM, Li X, Cocklin RR, Wang M, Wang M, Fukase K, Inamura S, Kusumoto S, Gupta D, Dziarski R (2003) Human peptidoglycan recognition protein-L is an N-acetylmuramoyl-L-alanine amidase. J Biol Chem 278:49044–49052

    Article  PubMed  CAS  Google Scholar 

  110. Xu M, Wang Z, Locksley RM (2004) Innate immune responses in peptidoglycan recognition protein L-deficient mice. Mol Cell Biol 24:7949–7957

    Article  PubMed  CAS  Google Scholar 

  111. Gomez MI, Lee A, Reddy B, Muir A, Soong G, Pitt A, Cheung A, Prince A (2004) Staphylococcus aureus protein A induces airway epithelial inflammatory responses by activating TNFR1. Nat Med 10:842–848

    Article  PubMed  CAS  Google Scholar 

  112. Classen A, Kalali BN, Schnopp C, Andres C, Aguilar-Pimentel JA, Ring J, Ollert M, Mempel M (2011) TNF receptor I on human keratinocytes is a binding partner for staphylococcal protein A resulting in the activation of NF kappa B, AP-1, and downstream gene transcription. Exp Dermatol 20:48–52

    Article  PubMed  CAS  Google Scholar 

  113. Casanova JL, Abel L, Quintana-Murci L (2011) Human TLRs and IL-1Rs in host defense: natural insights from evolutionary, epidemiological, and clinical genetics. Annu Rev Immunol 29:447–491

    Article  PubMed  CAS  Google Scholar 

  114. Schroder K, Tschopp J (2010) The inflammasomes. Cell 140:821–832

    Article  PubMed  CAS  Google Scholar 

  115. Miller LS, Pietras EM, Uricchio LH, Hirano K, Rao S, Lin H, O'Connell RM, Iwakura Y, Cheung AL, Cheng G, Modlin RL (2007) Inflammasome-mediated production of IL-1beta is required for neutrophil recruitment against Staphylococcus aureus in vivo. J Immunol 179:6933–6942

    PubMed  CAS  Google Scholar 

  116. Munoz-Planillo R, Franchi L, Miller LS, Nunez G (2009) A critical role for hemolysins and bacterial lipoproteins in Staphylococcus aureus-induced activation of the Nlrp3 inflammasome. J Immunol 183:3942–3948

    Article  PubMed  CAS  Google Scholar 

  117. Craven RR, Gao X, Allen IC, Gris D, Bubeck WJ, McElvania-Tekippe E, Ting JP, Duncan JA (2009) Staphylococcus aureus alpha-hemolysin activates the NLRP3-inflammasome in human and mouse monocytic cells. PLoS One 4:e7446

    Article  PubMed  CAS  Google Scholar 

  118. Shimada T, Park BG, Wolf AJ, Brikos C, Goodridge HS, Becker CA, Reyes CN, Miao EA, Aderem A, Gotz F, Liu GY, Underhill DM (2010) Staphylococcus aureus evades lysozyme-based peptidoglycan digestion that links phagocytosis, inflammasome activation, and IL-1beta secretion. Cell Host Microbe 7:38–49

    Article  PubMed  CAS  Google Scholar 

  119. Cho JS, Zussman J, Donegan NP, Ramos RI, Garcia NC, Uslan DZ, Iwakura Y, Simon SI, Cheung AL, Modlin RL, Kim J, Miller LS (2011) Noninvasive in vivo imaging to evaluate immune responses and antimicrobial therapy against Staphylococcus aureus and USA300 MRSA skin infections. J Invest Dermatol 131:907–915

    Article  PubMed  CAS  Google Scholar 

  120. Olaru F, Jensen LE (2010) Staphylococcus aureus stimulates neutrophil targeting chemokine expression in keratinocytes through an autocrine IL-1alpha signaling loop. J Invest Dermatol 130:1866–1876

    Article  PubMed  CAS  Google Scholar 

  121. Holtfreter S, Kolata J, Broker BM (2010) Towards the immune proteome of Staphylococcus aureus—the anti-S. aureus antibody response. Int J Med Microbiol 300:176–192

    Article  PubMed  CAS  Google Scholar 

  122. Kobayashi SD, Deleo FR (2011) A MRSA-terious enemy among us: boosting MRSA vaccines. Nat Med 17:168–169

    Article  PubMed  CAS  Google Scholar 

  123. Shinefield H, Black S, Fattom A, Horwith G, Rasgon S, Ordonez J, Yeoh H, Law D, Robbins JB, Schneerson R, Muenz L, Fuller S, Johnson J, Fireman B, Alcorn H, Naso R (2002) Use of a Staphylococcus aureus conjugate vaccine in patients receiving hemodialysis. N Engl J Med 346:491–496

    Article  PubMed  Google Scholar 

  124. DeJonge M, Burchfield D, Bloom B, Duenas M, Walker W, Polak M, Jung E, Millard D, Schelonka R, Eyal F, Morris A, Kapik B, Roberson D, Kesler K, Patti J, Hetherington S (2007) Clinical trial of safety and efficacy of INH-A21 for the prevention of nosocomial staphylococcal bloodstream infection in premature infants. J Pediatr 151:260–265

    Article  PubMed  CAS  Google Scholar 

  125. Miller LG, Quan C, Shay A, Mostafaie K, Bharadwa K, Tan N, Matayoshi K, Cronin J, Tan J, Tagudar G, Bayer AS (2007) A prospective investigation of outcomes after hospital discharge for endemic, community-acquired methicillin-resistant and -susceptible Staphylococcus aureus skin infection. Clin Infect Dis 44:483–492

    Article  PubMed  Google Scholar 

  126. Huang SS, Platt R (2003) Risk of methicillin-resistant Staphylococcus aureus infection after previous infection or colonization. Clin Infect Dis 36:281–285

    Article  PubMed  Google Scholar 

  127. Nguyen DM, Mascola L, Brancoft E (2005) Recurring methicillin-resistant Staphylococcus aureus infections in a football team. Emerg Infect Dis 11:526–532

    PubMed  Google Scholar 

  128. Deresinski S, Herrera V (2010) Immunotherapies for Staphylococcus aureus: current challenges and future prospects. Infect Control Hosp Epidemiol 31(Suppl 1):S45–S47

    Article  PubMed  Google Scholar 

  129. Schaffer AC, Lee JC (2008) Vaccination and passive immunisation against Staphylococcus aureus. Int J Antimicrob Agents 32(Suppl 1):S71–S78

    Article  PubMed  CAS  Google Scholar 

  130. Kennedy AD, Bubeck WJ, Gardner DJ, Long D, Whitney AR, Braughton KR, Schneewind O, Deleo FR (2010) Targeting of a-hemolysin by active or passive immunization decreases severity of USA300 skin infection in a mouse model. J Infect Dis 202:1050–1058

    Article  PubMed  Google Scholar 

  131. Bubeck WJ, Schneewind O (2008) Vaccine protection against Staphylococcus aureus pneumonia. J Exp Med 205:287–294

    Article  CAS  Google Scholar 

  132. Brown EL, Dumitrescu O, Thomas D, Badiou C, Koers EM, Choudhury P, Vazquez V, Etienne J, Lina G, Vandenesch F, Bowden MG (2009) The Panton–Valentine leukocidin vaccine protects mice against lung and skin infections caused by Staphylococcus aureus USA300. Clin Microbiol Infect 15:156–164

    Article  CAS  Google Scholar 

  133. Kim HK, Cheng AG, Kim HY, Missiakas DM, Schneewind O (2010) Nontoxigenic protein A vaccine for methicillin-resistant Staphylococcus aureus infections in mice. J Exp Med 207:1863–1870

    Article  PubMed  CAS  Google Scholar 

  134. Harro C, Betts R, Orenstein W, Kwak EJ, Greenberg HE, Onorato MT, Hartzel J, Lipka J, DiNubile MJ, Kartsonis N (2010) Safety and immunogenicity of a novel Staphylococcus aureus vaccine: results from the first study of the vaccine dose range in humans. Clin Vaccine Immunol 17:1868–1874

    Article  PubMed  CAS  Google Scholar 

  135. Cheng AG, McAdow M, Kim HK, Bae T, Missiakas DM, Schneewind O (2010) Contribution of coagulases towards Staphylococcus aureus disease and protective immunity. PLoS Pathog 6:e1001036

    Article  PubMed  CAS  Google Scholar 

  136. O'Shea JJ, Paul WE (2010) Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells. Science 327:1098–1102

    Article  PubMed  CAS  Google Scholar 

  137. Mathews WC, Caperna JC, Barber RE, Torriani FJ, Miller LG, May S, McCutchan JA (2005) Incidence of and risk factors for clinically significant methicillin-resistant Staphylococcus aureus infection in a cohort of HIV-infected adults. J Acquir Immune Defic Syndr 40:155–160

    Article  PubMed  Google Scholar 

  138. Skiest D, Brown K, Hester J, Moore T, Crosby C, Mussa HR, Hoffman-Roberts H, Cooper T (2006) Community-onset methicillin-resistant Staphylococcus aureus in an urban HIV clinic. HIV Med 7:361–368

    Article  PubMed  CAS  Google Scholar 

  139. Manfredi R, Calza L, Chiodo F (2002) Epidemiology and microbiology of cellulitis and bacterial soft tissue infection during HIV disease: a 10-year survey. J Cutan Pathol 29:168–172

    Article  PubMed  Google Scholar 

  140. McLoughlin RM, Solinga RM, Rich J, Zaleski KJ, Cocchiaro JL, Risley A, Tzianabos AO, Lee JC (2006) CD4+ T cells and CXC chemokines modulate the pathogenesis of Staphylococcus aureus wound infections. Proc Natl Acad Sci USA 103:10408–10413

    Article  PubMed  CAS  Google Scholar 

  141. Lin L, Ibrahim AS, Xu X, Farber JM, Avanesian V, Baquir B, Fu Y, French SW, Edwards JE Jr, Spellberg B (2009) Th1-Th17 cells mediate protective adaptive immunity against Staphylococcus aureus and Candida albicans infection in mice. PLoS Pathog 5:e1000703

    Article  PubMed  CAS  Google Scholar 

  142. Gaudreau MC, Lacasse P, Talbot BG (2007) Protective immune responses to a multi-gene DNA vaccine against Staphylococcus aureus. Vaccine 25:814–824

    Article  PubMed  CAS  Google Scholar 

  143. Zhao YX, Tarkowski A (1995) Impact of interferon-gamma receptor deficiency on experimental Staphylococcus aureus septicemia and arthritis. J Immunol 155:5736–5742

    PubMed  CAS  Google Scholar 

  144. Bieber T (2008) Atopic dermatitis. N Engl J Med 358:1483–1494

    Article  PubMed  CAS  Google Scholar 

  145. Cho SH, Strickland I, Tomkinson A, Fehringer AP, Gelfand EW, Leung DY (2001) Preferential binding of Staphylococcus aureus to skin sites of Th2-mediated inflammation in a murine model. J Invest Dermatol 116:658–663

    Article  PubMed  CAS  Google Scholar 

  146. Leung DY, Hauk P, Strickland I, Travers JB, Norris DA (1998) The role of superantigens in human diseases: therapeutic implications for the treatment of skin diseases. Br J Dermatol 139(Suppl 53):17–29

    Article  PubMed  CAS  Google Scholar 

  147. Laouini D, Kawamoto S, Yalcindag A, Bryce P, Mizoguchi E, Oettgen H, Geha RS (2003) Epicutaneous sensitization with superantigen induces allergic skin inflammation. J Allergy Clin Immunol 112:981–987

    Article  PubMed  CAS  Google Scholar 

  148. Cua DJ, Tato CM (2010) Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol 10:479–489

    Article  PubMed  CAS  Google Scholar 

  149. Korn T, Bettelli E, Oukka M, Kuchroo VK (2009) IL-17 and Th17 cells. Annu Rev Immunol 27:485–517

    Article  PubMed  CAS  Google Scholar 

  150. Peric M, Koglin S, Kim SM, Morizane S, Besch R, Prinz JC, Ruzicka T, Gallo RL, Schauber J (2008) IL-17A enhances vitamin D3-induced expression of cathelicidin antimicrobial peptide in human keratinocytes. J Immunol 181:8504–8512

    PubMed  CAS  Google Scholar 

  151. Liang SC, Tan XY, Luxenberg DP, Karim R, Dunussi-Joannopoulos K, Collins M, Fouser LA (2006) Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 203:2271–2279

    Article  PubMed  CAS  Google Scholar 

  152. Grimbacher B, Holland SM, Gallin JI, Greenberg F, Hill SC, Malech HL, Miller JA, O'Connell AC, Puck JM (1999) Hyper-IgE syndrome with recurrent infections—an autosomal dominant multisystem disorder. N Engl J Med 340:692–702

    Article  PubMed  CAS  Google Scholar 

  153. Minegishi Y, Saito M, Tsuchiya S, Tsuge I, Takada H, Hara T, Kawamura N, Ariga T, Pasic S, Stojkovic O, Metin A, Karasuyama H (2007) Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature 448:1058–1062

    Article  PubMed  CAS  Google Scholar 

  154. Holland SM, Deleo FR, Elloumi HZ, Hsu AP, Uzel G, Brodsky N, Freeman AF, Demidowich A, Davis J, Turner ML, Anderson VL, Darnell DN, Welch PA, Kuhns DB, Frucht DM, Malech HL, Gallin JI, Kobayashi SD, Whitney AR, Voyich JM, Musser JM, Woellner C, Schaffer AA, Puck JM, Grimbacher B (2007) STAT3 mutations in the hyper-IgE syndrome. N Engl J Med 357:1608–1619

    Article  PubMed  CAS  Google Scholar 

  155. Engelhardt KR, McGhee S, Winkler S, Sassi A, Woellner C, Lopez-Herrera G, Chen A, Kim HS, Lloret MG, Schulze I, Ehl S, Thiel J, Pfeifer D, Veelken H, Niehues T, Siepermann K, Weinspach S, Reisli I, Keles S, Genel F, Kutukculer N, Camcioglu Y, Somer A, Karakoc-Aydiner E, Barlan I, Gennery A, Metin A, Degerliyurt A, Pietrogrande MC, Yeganeh M, Baz Z, Al-Tamemi S, Klein C, Puck JM, Holland SM, McCabe ER, Grimbacher B, Chatila TA (2009) Large deletions and point mutations involving the dedicator of cytokinesis 8 (DOCK8) in the autosomal-recessive form of hyper-IgE syndrome. J Allergy Clin Immunol 124:1289–1302

    Article  PubMed  CAS  Google Scholar 

  156. Zhang Q, Davis JC, Lamborn IT, Freeman AF, Jing H, Favreau AJ, Matthews HF, Davis J, Turner ML, Uzel G, Holland SM, Su HC (2009) Combined immunodeficiency associated with DOCK8 mutations. N Engl J Med 361:2046–2055

    Article  PubMed  CAS  Google Scholar 

  157. Kisand K, Boe Wolff AS, Podkrajsek KT, Tserel L, Link M, Kisand KV, Ersvaer E, Perheentupa J, Erichsen MM, Bratanic N, Meloni A, Cetani F, Perniola R, Ergun-Longmire B, Maclaren N, Krohn KJ, Pura M, Schalke B, Strobel P, Leite MI, Battelino T, Husebye ES, Peterson P, Willcox N, Meager A (2010) Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines. J Exp Med 207:299–308

    Article  PubMed  CAS  Google Scholar 

  158. Puel A, Doffinger R, Natividad A, Chrabieh M, Barcenas-Morales G, Picard C, Cobat A, Ouachee-Chardin M, Toulon A, Bustamante J, Al-Muhsen S, Al-Owain M, Arkwright PD, Costigan C, McConnell V, Cant AJ, Abinun M, Polak M, Bougneres PF, Kumararatne D, Marodi L, Nahum A, Roifman C, Blanche S, Fischer A, Bodemer C, Abel L, Lilic D, Casanova JL (2010) Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I. J Exp Med 207:291–297

    Article  PubMed  CAS  Google Scholar 

  159. Puel A, Cypowyj S, Bustamante J, Wright JF, Liu L, Lim HK, Migaud M, Israel L, Chrabieh M, Audry M, Gumbleton M, Toulon A, Bodemer C, El-Baghdadi J, Whitters M, Paradis T, Brooks J, Collins M, Wolfman NM, Al-Muhsen S, Galicchio M, Abel L, Picard C, Casanova JL (2011) Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity. Science 332:65–68

    Article  PubMed  CAS  Google Scholar 

  160. Cecchinato V, Franchini G (2010) Th17 cells in pathogenic simian immunodeficiency virus infection of macaques. Curr Opin HIV AIDS 5:141–145

    Article  PubMed  Google Scholar 

  161. Favre D, Lederer S, Kanwar B, Ma ZM, Proll S, Kasakow Z, Mold J, Swainson L, Barbour JD, Baskin CR, Palermo R, Pandrea I, Miller CJ, Katze MG, McCune JM (2009) Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection. PLoS Pathog 5:e1000295

    Article  PubMed  CAS  Google Scholar 

  162. Hayashida S, Uchi H, Moroi Y, Furue M (2011) Decrease in circulating Th17 cells correlates with increased levels of CCL17, IgE and eosinophils in atopic dermatitis. J Dermatol Sci 61:180–186

    Article  PubMed  CAS  Google Scholar 

  163. Nograles KE, Zaba LC, Shemer A, Fuentes-Duculan J, Cardinale I, Kikuchi T, Ramon M, Bergman R, Krueger JG, Guttman-Yassky E (2009) IL-22-producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells. J Allergy Clin Immunol 123:1244–1252

    Article  PubMed  CAS  Google Scholar 

  164. Ishigame H, Kakuta S, Nagai T, Kadoki M, Nambu A, Komiyama Y, Fujikado N, Tanahashi Y, Akitsu A, Kotaki H, Sudo K, Nakae S, Sasakawa C, Iwakura Y (2009) Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity 30:108–119

    Article  PubMed  CAS  Google Scholar 

  165. Minegishi Y, Saito M, Nagasawa M, Takada H, Hara T, Tsuchiya S, Agematsu K, Yamada M, Kawamura N, Ariga T, Tsuge I, Karasuyama H (2009) Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome. J Exp Med 206:1291–1301

    Article  PubMed  CAS  Google Scholar 

  166. Cho JS, Pietras EM, Garcia NC, Ramos RI, Farzam DM, Monroe HR, Magorien JE, Blauvelt A, Kolls JK, Cheung AL, Cheng G, Modlin RL, Miller LS (2010) IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice. J Clin Invest 120:1762–1773

    Article  PubMed  Google Scholar 

  167. Girardi M (2006) Immunosurveillance and immunoregulation by gammadelta T cells. J Invest Dermatol 126:25–31

    Article  PubMed  CAS  Google Scholar 

  168. Villanueva E, Yalavarthi S, Berthier CC, Hodgin JB, Khandpur R, Lin AM, Rubin CJ, Zhao W, Olsen SH, Klinker M, Shealy D, Denny MF, Plumas J, Chaperot L, Kretzler M, Bruce AT, Kaplan MJ (2011) Netting neutrophils induce endothelial damage, infiltrate tissues, and expose immunostimulatory molecules in systemic lupus erythematosus. J Immunol 187:538–552

    Article  PubMed  CAS  Google Scholar 

  169. Lin AM, Rubin CJ, Khandpur R, Wang JY, Riblett M, Yalavarthi S, Villanueva EC, Shah P, Kaplan MJ, Bruce AT (2011) Mast cells and neutrophils release IL-17 through extracellular trap formation in psoriasis. J Immunol 187:490–500

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

L.S.M. is supported by the United States National Institutes of Health (R01 AI078910).

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This article is published as part of the Special Issue on Immunopathology of staphylococcal infections [34:3].

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Krishna, S., Miller, L.S. Innate and adaptive immune responses against Staphylococcus aureus skin infections. Semin Immunopathol 34, 261–280 (2012). https://doi.org/10.1007/s00281-011-0292-6

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