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Salmonella typhimurium-induced M1 macrophage polarization is dependent on the bacterial O antigen

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Abstract

Recently, macrophages were shown to be capable of differentiating toward two phenotypes after antigen stimulation: a classically activated (M1) or an alternatively activated phenotype (M2). To investigate the effect of Salmonella enteric serovar typhimurium (S. typhimurium) on macrophage differentiation, we compared macrophage phenotypes after infection of murine bone marrow-derived macrophages with wild-type S. typhimurium and its isogenic rfc mutant. S. typhimurium C5 induced M1 macrophage polarization and enhanced inducible nitric oxide synthase expression by macrophages; this induction was dependent on Toll-like receptor 4. In contrast, the Δrfc mutant (S. typhimurium C5 rfc::Kmr) lost this function and induced an M2 response in the macrophages. Here, we propose that S. typhimurium C5 is capable of polarizing macrophages towards the M1 phenotype and that this polarization is dependent on the O antigen encoded by rfc. Our finding indicates that M1 macrophage polarization induced by S. typhimurium may be related to the ability of this intracellular bacterium to survive and replicate within macrophages, which is essential for systemic disease.

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Abbreviations

BMMs:

Bone marrow-derived macrophages

CFU:

Colony forming units

IFN:

Interferon

IL:

Interleukine

iNOS:

Inducible nitric oxide synthase

Km:

Kanamycin

LPS:

Lipopolysaccharide

TGF:

Transforming growth factor

TLR:

Toll-like receptor

References

  • Benoit M, Desnues B, Mege JL (2008) Macrophage polarization in bacterial infections. J Immunol 181:3733–3739

    Article  CAS  Google Scholar 

  • Boldrick JC, Alizadeh AA, Diehn M, Dudoit S, Liu CL, Belcher CE, Botstein D, Staudt LM, Brown PO, Relman DA (2002) Stereotyped and specific gene expression programs in human innate immune responses to bacteria. Proc Natl Acad Sci USA 99:972–977

    Article  CAS  Google Scholar 

  • Collins LV, Attridge S, Hackett J (1991) Mutations at rfc or pmi attenuate Salmonella typhimurium virulence for mice. Infect Immun 59:1079–1085

    CAS  Google Scholar 

  • Du Y, Yang M, Wei W, Huynh HD, Herz J, Saghatelian A, Wan Y (2012) Macrophage VLDL receptor promotes PAFAH secretion in mother’s milk and suppresses systemic inflammationin nursing neonates. Nat Commun 3:1008

    Article  Google Scholar 

  • Eisele NA, Ruby T, Jacobson A, Manzanillo PS, Cox JS, Lam L, Mukundan L, Chawla A, Monack DM (2013) Salmonella require the fatty acid regulator PPARδ for the establishment of a metabolic environment essential for long-term persistence. Cell Host Microbe 14:171–182

    Article  CAS  Google Scholar 

  • Galli SJ, Borregaard N, Wynn TA (2011) Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils. Nat Immunol 12:1035–1044

    Article  CAS  Google Scholar 

  • Gordon S, Plűddemann A (2013) Tissue macrophage heterogeneity: issues and prospects. Semin Immunopathol 35:533–540

    Article  CAS  Google Scholar 

  • Gordon S, Taylor PR (2005) Monocyte and macrophage heterogeneity. Nat Rev Immunol 5:953–964

    Article  CAS  Google Scholar 

  • Hoffmann R, van Erp K, Trulzsch K, Heesemann J (2004) Transcriptional responses of murine macrophages to infection with Yersinia enterocolitica. Cell Microbiol 6:377–390

    Article  CAS  Google Scholar 

  • Mantovani A, Sozzani S, Locati M, Allavena P, Sica A (2002) Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 23:549–555

    Article  CAS  Google Scholar 

  • Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8:958–969

    Article  CAS  Google Scholar 

  • Nagy G, Palkovics T, Otto A, Kusch H, Kocsis B, Dobrindt U, Engelmann S, Hecker M, Emödy L, Pál T, Hacker J (2008) “Gently rough”: the vaccine potential of a Salmonella enterica regulatory lipopolysaccharide mutant. J Infect Dis 198:1699–1706

    Article  CAS  Google Scholar 

  • Nau GJ, Richmond JF, Schlesinger A, Jennings EG, Lander ES, Young RA (2002) Human macrophage activation programs induced by bacterial pathogens. Proc Natl Acad Sci USA 99:1503–1508

    Article  CAS  Google Scholar 

  • Raetz CRH, Whitfield C (2002) Lipopolysaccharide endotoxins. Annu Rev Biochem 71:635–700

    Article  CAS  Google Scholar 

  • Sica A, Mantovani A (2012) Macrophage plasticity and polarization: in vivo veritas. J Clin Invest 122:787–795

    Article  CAS  Google Scholar 

  • Stocker BAD, Makela PH (1978) Genetics of (gram-negative) bacterial surface. Proc R Soc Lond B Biol 202:5–30

    Article  CAS  Google Scholar 

  • Stocker BAD, Makela PH (1986) Genetic determination of bacterial virulence, with special reference to Salmonella. Curr Top Microbiol Immunol 124:149–172

    CAS  Google Scholar 

  • Stout RD, Jiang C, Matta B, Tietzel I, Watkins SK, Syttles J (2005) Macrophages sequentially change their functional phenotype in response to changes in microenvironmental influences. J Immunol 175:342–349

    Article  CAS  Google Scholar 

  • Tran AX, Whitfield C (2009) Lipopolysaccharides (endotoxins). Encyclopedia of microbiology. Academic Press, Oxford, pp 513–528

    Book  Google Scholar 

  • Whitfield C (1995) Biosynthesis of lipopolysaccharide o-antigens. Trends Microbiol 3:178–185

    Article  CAS  Google Scholar 

  • Zhang XL, Tsui IS, Yip CM, Fung AW, Wong DK, Dai X, Yang Y, Hackett J, Morris C (2000) Salmonella enterica serovar typhi uses type IVB pili to enter human intestinal epithelial cells. Infect Immun 68:3067–3073

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (31221061, 31270176 and 31370197), National Outstanding Youth Foundation of China (81025008), the 973 Program of China (2012CB720604),the Hubei Province’s Outstanding Medical Academic Leader Program (523-276003) and the Science and Technology Program of Wuhan (201150530141).

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Authors and Affiliations

  1. State Key Laboratory of Virology, Medical Research Institute of Wuhan University and Department of Immunology and Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University School of Medicine, Donghu Road 185#, Wuhan, 430071, Hubei Province, China

    Fengling Luo, Xiaoming Sun, Zhen Qu & Xiaolian Zhang

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  1. Fengling Luo
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  2. Xiaoming Sun
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  3. Zhen Qu
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  4. Xiaolian Zhang
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Correspondence to Xiaolian Zhang.

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Luo, F., Sun, X., Qu, Z. et al. Salmonella typhimurium-induced M1 macrophage polarization is dependent on the bacterial O antigen. World J Microbiol Biotechnol 32, 22 (2016). https://doi.org/10.1007/s11274-015-1978-z

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