Skip to main content

Advertisement

SpringerLink
Log in

Statin modulation of monocyte phenotype and function: implications for HIV-1-associated neurocognitive disorders

  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

HIV-1-associated neurocognitive disorder (HAND) remains a persistent problem despite antiretroviral therapy (ART), largely a result of continued inflammation in the periphery and the brain and neurotoxin release from activated myeloid cells in the CNS. CD14+CD16+ inflammatory monocytes, expanded in HIV infection, play a central role in the pathogenesis of HAND and have parallels with monocyte-dependent inflammatory mechanisms in atherosclerosis. Statins, through their HMG-CoA reductase inhibitor activity, have pleiotropic immunomodulatory properties that contribute to their benefit in atherosclerosis beyond lipid lowering. Here, we investigated whether statins would modulate the monocyte phenotype and function associated with HIV-1 neuropathogenesis. Treatment ex vivo with simvastatin and atorvastatin reduced the proportion of CD16+ monocytes in peripheral blood mononuclear cells, as well as in purified monocytes, especially CD14++CD16+ “intermediate” monocytes most closely associated with neurocognitive disease. Statin treatment also markedly reduced expression of CD163, which is also linked to HAND pathogenesis. Finally, simvastatin inhibited production of monocyte chemoattractant protein-1 (MCP-1) and other inflammatory cytokines following LPS stimulation and reduced monocyte chemotaxis in response to MCP-1, a major driver of myeloid cell accumulation in the CNS in HAND. Together, these findings suggest that statin drugs may be useful to prevent or reduce HAND in HIV-1-infected subjects on ART with persistent monocyte activation and inflammation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Aboyans V, Labrousse L et al (2006) Predictive factors of stroke in patients undergoing coronary bypass grafting: statins are protective. Eur J Cardiothorac Surg 30(2):300–304

    Article  PubMed  Google Scholar 

  • Almuti K, Rimawi R et al (2006) Effects of statins beyond lipid lowering: potential for clinical benefits. Int J Cardiol 109(1):7–15

    Article  PubMed  Google Scholar 

  • Ancuta P, Autissier P et al (2006a) CD16+ monocyte-derived macrophages activate resting T cells for HIV infection by producing CCR3 and CCR4 ligands. J Immunol 176(10):5760–5771

    Article  CAS  PubMed  Google Scholar 

  • Ancuta P, Kunstman KJ et al (2006b) CD16+ monocytes exposed to HIV promote highly efficient viral replication upon differentiation into macrophages and interaction with T cells. Virology 344(2):267–276

    Article  CAS  PubMed  Google Scholar 

  • Ancuta P, Wang J et al (2006c) CD16+ monocytes produce IL-6, CCL2, and matrix metalloproteinase-9 upon interaction with CX3CL1-expressing endothelial cells. J Leukoc Biol 80(5):1156–1164

    Article  CAS  PubMed  Google Scholar 

  • Bastard JP, Soulie C et al (2012) Circulating interleukin-6 levels correlate with residual HIV viraemia and markers of immune dysfunction in treatment-controlled HIV-infected patients. Antivir Ther 17(5):915–919

    Article  CAS  PubMed  Google Scholar 

  • Borda JT, Alvarez X et al (2008) CD163, a marker of perivascular macrophages, is up-regulated by microglia in simian immunodeficiency virus encephalitis after haptoglobin-hemoglobin complex stimulation and is suggestive of breakdown of the blood-brain barrier. Am J Pathol 172(3):725–737

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bruegel M, Teupser D et al (2006) Statins reduce macrophage inflammatory protein-1alpha expression in human activated monocytes. Clin Exp Pharmacol Physiol 33(12):1144–1149

    Article  CAS  PubMed  Google Scholar 

  • Burdo TH, Weiffenbach A et al (2013) Elevated sCD163 in plasma but not cerebrospinal fluid is a marker of neurocognitive impairment in HIV infection. AIDS 27(9):1387–1395

    Article  CAS  PubMed  Google Scholar 

  • Chen MF, Gill AJ et al (2014) Neuropathogenesis of HIV-associated neurocognitive disorders: roles for immune activation, HIV blipping and viral tropism. Curr Opin HIV AIDS 9(6):559–564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cinque P, Vago L et al (1998) Elevated cerebrospinal fluid levels of monocyte chemotactic protein-1 correlate with HIV-1 encephalitis and local viral replication. AIDS 12(11):1327–1332

    Article  CAS  PubMed  Google Scholar 

  • Clay CC, Rodrigues DS et al (2007) Neuroinvasion of fluorescein-positive monocytes in acute simian immunodeficiency virus infection. J Virol 81(21):12040–12048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Wit S, Delforge M et al (2011) Downregulation of CD38 activation markers by atorvastatin in HIV patients with undetectable viral load. Aids 25(10):1332–1333

    Article  PubMed  Google Scholar 

  • d’Ettorre G, Paiardini M et al (2011) HIV persistence in the gut mucosa of HIV-infected subjects undergoing antiretroviral therapy correlates with immune activation and increased levels of LPS. Curr HIV Res 9(3):148–153

    Article  PubMed  Google Scholar 

  • Dhillon NK, Williams R et al (2008) Roles of MCP-1 in development of HIV-dementia. Front Biosci 13:3913–3918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ellery PJ, Tippett E et al (2007) The CD16+ monocyte subset is more permissive to infection and preferentially harbors HIV-1 in vivo. J Immunol 178(10):6581–6589

    Article  CAS  PubMed  Google Scholar 

  • Ellis RJ, Badiee J et al (2011) CD4 nadir is a predictor of HIV neurocognitive impairment in the era of combination antiretroviral therapy. AIDS 25(14):1747–1751

    Article  CAS  PubMed  Google Scholar 

  • Eugenin EA, Osiecki K et al (2006) CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood-brain barrier: a potential mechanism of HIV-CNS invasion and NeuroAIDS. J Neurosci 26(4):1098–1106

    Article  CAS  PubMed  Google Scholar 

  • Everett BM, Glynn RJ et al (2010) Rosuvastatin in the prevention of stroke among men and women with elevated levels of C-reactive protein: justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER). Circulation 121(1):143–150

    Article  CAS  PubMed  Google Scholar 

  • Fabriek BO, van Bruggen R et al (2009) The macrophage scavenger receptor CD163 functions as an innate immune sensor for bacteria. Blood 113(4):887–892

    Article  CAS  PubMed  Google Scholar 

  • Fischer-Smith T, Croul S et al (2001) CNS invasion by CD14+/CD16+ peripheral blood-derived monocytes in HIV dementia: perivascular accumulation and reservoir of HIV infection. J Neurovirol 7(6):528–541

    Article  CAS  PubMed  Google Scholar 

  • Fischer-Smith T, Bell C et al (2008) Monocyte/macrophage trafficking in acquired immunodeficiency syndrome encephalitis: lessons from human and nonhuman primate studies. J Neurovirol 14(4):318–326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Funderburg NT, Jiang Y et al (2014) Rosuvastatin treatment reduces markers of monocyte activation in HIV-infected subjects on antiretroviral therapy. Clin Infect Dis 58(4):588–595

    Article  CAS  PubMed  Google Scholar 

  • Funderburg NT, Jiang Y et al (2015) Rosuvastatin reduces vascular inflammation and T-cell and monocyte activation in HIV-infected subjects on antiretroviral therapy. J Acquir Immune Defic Syndr 68(4):396–404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ganesan A, Crum-Cianflone N et al (2011) High dose atorvastatin decreases cellular markers of immune activation without affecting HIV-1 RNA levels: results of a double-blind randomized placebo controlled clinical trial. J Infect Dis 203(6):756–764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Glass JD, Fedor H et al (1995) Immunocytochemical quantitation of human immunodeficiency virus in the brain: correlations with dementia. Ann Neurol 38(5):755–762

    Article  CAS  PubMed  Google Scholar 

  • Graversen JH, Madsen M et al (2002) CD163: a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma. Int J Biochem Cell Biol 34(4):309–314

    Article  CAS  PubMed  Google Scholar 

  • Han KH, Ryu J et al (2005) HMG-CoA reductase inhibition reduces monocyte CC chemokine receptor 2 expression and monocyte chemoattractant protein-1-mediated monocyte recruitment in vivo. Circulation 111(11):1439–1447

    Article  CAS  PubMed  Google Scholar 

  • Hodgkinson CP, Ye S (2008) Statins inhibit toll-like receptor 4-mediated lipopolysaccharide signaling and cytokine expression. Pharmacogenet Genomics 18(9):803–813

    Article  CAS  PubMed  Google Scholar 

  • Isoda K, Folco E et al (2008) Glycated LDL increases monocyte CC chemokine receptor 2 expression and monocyte chemoattractant protein-1-mediated chemotaxis. Atherosclerosis 198(2):307–312

    Article  CAS  PubMed  Google Scholar 

  • Jaworowski A, Kamwendo DD et al (2007) CD16+ monocyte subset preferentially harbors HIV-1 and is expanded in pregnant Malawian women with Plasmodium falciparum malaria and HIV-1 infection. J Infect Dis 196(1):38–42

    Article  CAS  PubMed  Google Scholar 

  • Jialal I, Stein D et al (2001) Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high sensitive C-reactive protein levels. Circulation 103(15):1933–1935

    Article  CAS  PubMed  Google Scholar 

  • Jiang W, Lederman MM et al (2009) Plasma levels of bacterial DNA correlate with immune activation and the magnitude of immune restoration in persons with antiretroviral-treated HIV infection. J Infect Dis 199(8):1177–1185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kamat A, Lyons JL et al (2012) Monocyte activation markers in cerebrospinal fluid associated with impaired neurocognitive testing in advanced HIV infection. J Acquir Immune Defic Syndr 60(3):234–243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim WK, Alvarez X et al (2006) CD163 identifies perivascular macrophages in normal and viral encephalitic brains and potential precursors to perivascular macrophages in blood. Am J Pathol 168(3):822–834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kristiansen M, Graversen JH et al (2001) Identification of the haemoglobin scavenger receptor. Nature 409(6817):198–201

    Article  CAS  PubMed  Google Scholar 

  • Lane BR, Lore K et al (2001) Interleukin-8 stimulates human immunodeficiency virus type 1 replication and is a potential new target for antiretroviral therapy. J Virol 75(17):8195–8202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Letendre SL, Marquie-Beck J et al (2007) The role of cohort studies in drug development: clinical evidence of antiviral activity of serotonin reuptake inhibitors and HMG-CoA reductase inhibitors in the central nervous system. J Neuroimmune Pharmacol 2(1):120–127

    Article  PubMed  Google Scholar 

  • Letendre SL, Zheng JC et al (2011) Chemokines in cerebrospinal fluid correlate with cerebral metabolite patterns in HIV-infected individuals. J Neurovirol 17(1):63–69

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liang H, Duan Z, et al (2015) Higher levels of circulating monocyte-platelet aggregates are correlated with viremia and increased sCD163 levels in HIV-1 infection. Cell Mol Immunol 12(4):435–443

  • Longenecker CT, Hileman CO et al (2014) Rosuvastatin preserves renal function and lowers cystatin C in HIV-infected subjects on antiretroviral therapy: the SATURN-HIV trial. Clin Infect Dis 59(8):1148–1156

    Article  PubMed  PubMed Central  Google Scholar 

  • Mamik MK, Ghorpade A (2014) Chemokine CXCL8 promotes HIV-1 replication in human monocyte-derived macrophages and primary microglia via nuclear factor-kappaB pathway. PLoS One 9(3):e92145

    Article  PubMed  PubMed Central  Google Scholar 

  • Marino F, Maresca AM et al (2014) Simvastatin down-regulates the production of Interleukin-8 by neutrophil leukocytes from dyslipidemic patients. BMC Cardiovasc Disord 14:37

    Article  PubMed  PubMed Central  Google Scholar 

  • McCombe JA, Vivithanaporn P et al (2013) Predictors of symptomatic HIV-associated neurocognitive disorders in universal health care. HIV Med 14(2):99–107

    Article  CAS  PubMed  Google Scholar 

  • McKibben RA, Margolick JB et al (2015) Elevated levels of monocyte activation markers are associated with subclinical atherosclerosis in men with and those without HIV infection. J Infect Dis 211(8):1219–1228

    PubMed  Google Scholar 

  • Methe H, Kim JO et al (2005) Statins decrease Toll-like receptor 4 expression and downstream signaling in human CD14+ monocytes. Arterioscler Thromb Vasc Biol 25(7):1439–1445

    Article  CAS  PubMed  Google Scholar 

  • Moller HJ (2012) Soluble CD163. Scand J Clin Lab Invest 72(1):1–13

    Article  CAS  PubMed  Google Scholar 

  • Montecucco F, Burger F et al (2009) Statins inhibit C-reactive protein-induced chemokine secretion, ICAM-1 upregulation and chemotaxis in adherent human monocytes. Rheumatology (Oxford) 48(3):233–242

    Article  CAS  Google Scholar 

  • Mothobi NZ, Brew BJ (2012) Neurocognitive dysfunction in the highly active antiretroviral therapy era. Curr Opin Infect Dis 25(1):4–9

    Article  CAS  PubMed  Google Scholar 

  • Munoz-Moreno JA, Fumaz CR et al (2008) Nadir CD4 cell count predicts neurocognitive impairment in HIV-infected patients. AIDS Res Hum Retroviruses 24(10):1301–1307

    Article  CAS  PubMed  Google Scholar 

  • Namiki M, Kawashima S et al (2002) Local overexpression of monocyte chemoattractant protein-1 at vessel wall induces infiltration of macrophages and formation of atherosclerotic lesion: synergism with hypercholesterolemia. Arterioscler Thromb Vasc Biol 22(1):115–120

    Article  CAS  PubMed  Google Scholar 

  • Ndhlovu LC, Umaki T et al (2014) Treatment intensification with maraviroc (CCR5 antagonist) leads to declines in CD16-expressing monocytes in cART-suppressed chronic HIV-infected subjects and is associated with improvements in neurocognitive test performance: implications for HIV-associated neurocognitive disease (HAND). J Neurovirol 20(6):571–582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Niessner A, Steiner S et al (2006) Simvastatin suppresses endotoxin-induced upregulation of toll-like receptors 4 and 2 in vivo. Atherosclerosis 189(2):408–413

    Article  CAS  PubMed  Google Scholar 

  • Park IW, Wang JF et al (2001) HIV-1 Tat promotes monocyte chemoattractant protein-1 secretion followed by transmigration of monocytes. Blood 97(2):352–358

    Article  CAS  PubMed  Google Scholar 

  • Pasceri V, Cheng JS et al (2001) Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation 103(21):2531–2534

    Article  CAS  PubMed  Google Scholar 

  • Piconi S, Trabattoni D et al (2010) Immune activation, apoptosis, and Treg activity are associated with persistently reduced CD4+ T-cell counts during antiretroviral therapy. AIDS 24(13):1991–2000

    Article  CAS  PubMed  Google Scholar 

  • Pierdominici M, Giovannetti A et al (2002) Changes in CCR5 and CXCR4 expression and beta-chemokine production in HIV-1-infected patients treated with highly active antiretroviral therapy. J Acquir Immune Defic Syndr 29(2):122–131

    Article  CAS  PubMed  Google Scholar 

  • Pilakka-Kanthikeel S, Kris A et al (2014) Immune activation is associated with increased gut microbial translocation in treatment-naive, HIV-infected children in a resource-limited setting. J Acquir Immune Defic Syndr 66(1):16–24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pozo M, de Nicolas R et al (2006) Simvastatin inhibits the migration and adhesion of monocytic cells and disorganizes the cytoskeleton of activated endothelial cells. Eur J Pharmacol 548(1-3):53–63

    Article  CAS  PubMed  Google Scholar 

  • Probasco JC, Spudich SS et al (2008) Failure of atorvastatin to modulate CSF HIV-1 infection: results of a pilot study. Neurology 71(7):521–524

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ragin AB, Wu Y et al (2006) Monocyte chemoattractant protein-1 correlates with subcortical brain injury in HIV infection. Neurology 66(8):1255–1257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rallidis LS, Hamodraka ES et al (2008) Simvastatin exerts its anti-inflammatory effect in hypercholesterolaemic patients by decreasing the serum levels of monocyte chemoattractant protein-1. Int J Cardiol 124(2):271–272

    Article  PubMed  Google Scholar 

  • Rantapaa-Dahlqvist S, Boman K et al (2007) Up regulation of monocyte chemoattractant protein-1 expression in anti-citrulline antibody and immunoglobulin M rheumatoid factor positive subjects precedes onset of inflammatory response and development of overt rheumatoid arthritis. Ann Rheum Dis 66(1):121–123

    Article  CAS  PubMed  Google Scholar 

  • Roberts ES, Masliah E et al (2004) CD163 identifies a unique population of ramified microglia in HIV encephalitis (HIVE). J Neuropathol Exp Neurol 63(12):1255–1264

    Article  PubMed  Google Scholar 

  • Schaer CA, Vallelian F et al (2007) CD163-expressing monocytes constitute an endotoxin-sensitive Hb clearance compartment within the vascular system. J Leukoc Biol 82(1):106–110

    Article  CAS  PubMed  Google Scholar 

  • Schepers A, Eefting D et al (2006) Anti-MCP-1 gene therapy inhibits vascular smooth muscle cells proliferation and attenuates vein graft thickening both in vitro and in vivo. Arterioscler Thromb Vasc Biol 26(9):2063–2069

    Article  CAS  PubMed  Google Scholar 

  • Shan L, Siliciano RF (2014) Unraveling the relationship between microbial translocation and systemic immune activation in HIV infection. J Clin Invest 124(6):2368–2371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sulicka J, Surdacki A et al (2013) Elevated markers of inflammation and endothelial activation and increased counts of intermediate monocytes in adult survivors of childhood acute lymphoblastic leukemia. Immunobiology 218(5):810–816

    Article  CAS  PubMed  Google Scholar 

  • Tippett E, Cheng WJ et al (2011) Differential expression of CD163 on monocyte subsets in healthy and HIV-1 infected individuals. PLoS One 6(5):e19968

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Valcour VG, Shiramizu BT et al (2010) HIV DNA in circulating monocytes as a mechanism to dementia and other HIV complications. J Leukoc Biol 87(4):621–626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vassallo M, Mercie P et al (2012) The role of lipopolysaccharide as a marker of immune activation in HIV-1 infected patients: a systematic literature review. Virol J 9:174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Veillard NR, Braunersreuther V et al (2006) Simvastatin modulates chemokine and chemokine receptor expression by geranylgeranyl isoprenoid pathway in human endothelial cells and macrophages. Atherosclerosis 188(1):51–58

    Article  CAS  PubMed  Google Scholar 

  • Wada NI, Jacobson LP et al (2015) The effect of HAART-induced HIV suppression on circulating markers of inflammation and immune activation. AIDS 29(4):463–471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wallet MA, Rodriguez CA et al (2010) Microbial translocation induces persistent macrophage activation unrelated to HIV-1 levels or T-cell activation following therapy. AIDS 24(9):1281–1290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang ZM, Liu C et al (2000) Chemokines are the main proinflammatory mediators in human monocytes activated by Staphylococcus aureus, peptidoglycan, and endotoxin. J Biol Chem 275(27):20260–20267

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Zou H et al (2006) The expression of monocyte chemoattractant protein-1 and C-C chemokine receptor 2 in post-kidney transplant patients and the influence of simvastatin treatment. Clin Chim Acta 373(1-2):44–48

    Article  CAS  PubMed  Google Scholar 

  • Wang H, Sun J et al (2008) Human immunodeficiency virus type 1 infection increases the in vivo capacity of peripheral monocytes to cross the blood-brain barrier into the brain and the in vivo sensitivity of the blood-brain barrier to disruption by lipopolysaccharide. J Virol 82(15):7591–7600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Z, Zheng Y et al (2013) High prevalence of HIV-associated neurocognitive disorder in HIV-infected patients with a baseline CD4 count </= 350 cells/muL in Shanghai, China. Biosci Trends 7(6):284–289

    PubMed  Google Scholar 

  • Watkins CC, Treisman GJ (2015) Cognitive impairment in patients with AIDS - prevalence and severity. HIV AIDS (Auckl) 7:35–47

    Google Scholar 

  • Williams DW, Veenstra M et al (2014) Monocytes mediate HIV neuropathogenesis: mechanisms that contribute to HIV associated neurocognitive disorders. Curr HIV Res 12(2):85–96

  • Williams DW, Eugenin EA et al (2012) Monocyte maturation, HIV susceptibility, and transmigration across the blood brain barrier are critical in HIV neuropathogenesis. J Leukoc Biol 91(3):401–415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Williams DW, Calderon TM et al (2013) Mechanisms of HIV entry into the CNS: increased sensitivity of HIV infected CD14 + CD16+ monocytes to CCL2 and key roles of CCR2, JAM-A, and ALCAM in diapedesis. PLoS One 8(7):e69270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilson EM, Singh A et al (2014) Monocyte-activation phenotypes are associated with biomarkers of inflammation and coagulation in chronic HIV infection. J Infect Dis 210(9):1396–1406

    Article  PubMed  PubMed Central  Google Scholar 

  • Yadav A, Collman RG (2009) CNS inflammation and macrophage/microglial biology associated with HIV-1 infection. J Neuroimmune Pharmacol 4(4):430–447

    Article  PubMed  Google Scholar 

  • Yuan L, Qiao L et al (2013) Cytokines in CSF correlate with HIV-associated neurocognitive disorders in the post-HAART era in China. J Neurovirol 19(2):144–149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuan L, Liu A et al (2015) The relationship of CSF and plasma cytokine levels in HIV infected patients with neurocognitive impairment. Biomed Res Int 2015:506872

    PubMed  PubMed Central  Google Scholar 

  • Zanin V, Delbue S et al (2012) Specific protein profile in cerebrospinal fluid from HIV-1-positive cART-treated patients affected by neurological disorders. J Neurovirol 18(5):416–422

    Article  CAS  PubMed  Google Scholar 

  • Zawada AM, Rogacev KS et al (2011) SuperSAGE evidence for CD14++CD16+ monocytes as a third monocyte subset. Blood 118(12):e50–e61

    Article  CAS  PubMed  Google Scholar 

  • Zhou H, Lapointe BM et al (2006) A requirement for microglial TLR4 in leukocyte recruitment into brain in response to lipopolysaccharide. J Immunol 177(11):8103–8110

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank D. Carnathan, G. Makedonas, C. Pombo, and K. Demers for assistance with flow cytometry and members of the Collman lab for critical input and advice. This work was supported by NIH grant MH061139 to R.G.C, and we acknowledge assistance from multiple Cores of the Penn Center for AIDS Research (P30-AI045008).

Author information

Authors and Affiliations

  1. Department of Medicine, University of Pennsylvania Perelman School of Medicine, 36th and Hamilton Walk, Philadelphia, PA, 19104, USA

    Anjana Yadav & Ronald G. Collman

  2. Department of Microbiology, University of Pennsylvania Perelman School of Medicine, 36th and Hamilton Walk, Philadelphia, PA, 19104, USA

    Michael R. Betts & Ronald G. Collman

Authors
  1. Anjana Yadav
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael R. Betts
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ronald G. Collman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ronald G. Collman.

Ethics declarations

Conflict of interest

The authors A. Yadav, M.R. Betts, and R.G. Collman declare that they have no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 1152 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yadav, A., Betts, M.R. & Collman, R.G. Statin modulation of monocyte phenotype and function: implications for HIV-1-associated neurocognitive disorders. J. Neurovirol. 22, 584–596 (2016). https://doi.org/10.1007/s13365-016-0433-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13365-016-0433-8

Keywords

Search

Navigation