Abstract
Increased levels of monocyte–platelet aggregates (MPAs) are reported to be highly correlated with cardiovascular events. In this study, the MPA levels in different monocyte subsets and the associations between MPA levels, HIV-1 viremia and monocyte activation were evaluated during HIV-1 infection. The results showed that the percentages of MPAs in all three monocyte subsets were higher in HIV-1-infected subjects than in healthy controls, and were associated with the plasma viral load in the non-classical and intermediate monocyte subsets. The plasma levels of sCD14 and sCD163 were upregulated in HIV-1 infection and were positively associated with viral loads and negatively associated with CD4 counts. P-selectin glycoprotein ligand-1 (PSGL-1) was shown to be expressed at significantly lower levels on all three monocyte subsets and was negatively correlated with the sCD163 level. The MPA level was correlated with the levels of plasma sCD163 but negatively correlated with CD163 and PSGL-1 on all three monocyte subsets. An elevated immune activation status was correlated with increased MPA formation, underlying the potential interaction between monocyte activation and MPA formation. This interaction may be related to a higher thromboembolic risk in patients infected with HIV-1.
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References
Burdo TH, Lentz MR, Autissier P, Krishnan A, Halpern E, Letendre S et al. Soluble CD163 made by monocyte/macrophages is a novel marker of HIV activity in early and chronic infection prior to and after anti-retroviral therapy. J Infect Dis 2011; 204: 154–163.
Burdo TH, Lo J, Abbara S, Wei J, DeLelys ME, Preffer F et al. Soluble CD163, a novel marker of activated macrophages, is elevated and associated with noncalcified coronary plaque in HIV-infected patients. J Infect Dis 2011; 204: 1227–1236.
Chevalier MF, Petitjean G, Dunyach-Remy C, Didier C, Girard PM, Manea ME et al. The Th17/Treg ratio, IL-1RA and sCD14 levels in primary HIV infection predict the T-cell activation set point in the absence of systemic microbial translocation. PLoS Pathog 2013; 9: e1003453.
Knudsen A, Moller HJ, Katzenstein TL, Gerstoft J, Obel N, Kronborg G et al. Soluble CD163 does not predict first-time myocardial infarction in patients infected with human immunodeficiency virus: a nested case–control study. BMC Infect Dis 2013; 13: 230.
Leeansyah E, Malone DF, Anthony DD, Sandberg JK . Soluble biomarkers of HIV transmission, disease progression and comorbidities. Curr Opin HIV AIDS 2013; 8: 117–124.
Sandler NG, Wand H, Roque A, Law M, Nason MC, Nixon DE et al. Plasma levels of soluble CD14 independently predict mortality in HIV infection. J Infect Dis 2011; 203: 780–790.
Dolganiuc A, Garcia C, Kodys K, Szabo G . Distinct Toll-like receptor expression in monocytes and T cells in chronic HCV infection. World J Gastroenterol 2006; 12: 1198–1204.
Ma Y, He B . Recognition of herpes simplex viruses: Toll-like receptors and beyond. J Mol Biol 2014; 426: 1133–1147.
Arpaia N, Barton GM . Toll-like receptors: key players in antiviral immunity. Curr Opin Virol 2011; 1: 447–454.
Lester RT, Yao XD, Ball TB, McKinnon LR, Kaul R, Wachihi C et al. Toll-like receptor expression and responsiveness are increased in viraemic HIV-1 infection. AIDS 2008; 22: 685–694.
Meier A, Bagchi A, Sidhu HK, Alter G, Suscovich TJ, Kavanagh DG et al. Upregulation of PD-L1 on monocytes and dendritic cells by HIV-1 derived TLR ligands. AIDS 2008; 22: 655–658.
Rodriguez-Garcia M, Porichis F, de Jong OG, Levi K, Diefenbach TJ, Lifson JD et al. Expression of PD-L1 and PD-L2 on human macrophages is up-regulated by HIV-1 and differentially modulated by IL-10. J Leukoc Biol 2011; 89: 507–515.
Ziegler-Heitbrock L, Ancuta P, Crowe S, Dalod M, Grau V, Hart DN et al. Nomenclature of monocytes and dendritic cells in blood. Blood 2010; 116: e74–e80.
van de Veerdonk FL, Netea MG . Diversity: a hallmark of monocyte society. Immunity 2010; 33: 289–291.
Cros J, Cagnard N, Woollard K, Patey N, Zhang SY, Senechal B et al. Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors. Immunity 2010; 33: 375–386.
Han J, Wang B, Han N, Zhao Y, Song C, Feng X et al. CD14highCD16+ rather than CD14lowCD16+ monocytes correlate with disease progression in chronic HIV-infected patients. J Acquir Immune Defic Syndr 2009; 52: 553–559.
Funderburg NT, Zidar DA, Shive C, Lioi A, Mudd J, Musselwhite LW et al. Shared monocyte subset phenotypes in HIV-1 infection and in uninfected subjects with acute coronary syndrome. Blood 2012; 120: 4599–4608.
Shantsila E, Lip GY . The role of monocytes in thrombotic disorders. Insights from tissue factor, monocyte–platelet aggregates and novel mechanisms. Thromb Haemost 2009; 102: 916–924.
Furman MI, Barnard MR, Krueger LA, Fox ML, Shilale EA, Lessard DM et al. Circulating monocyte-platelet aggregates are an early marker of acute myocardial infarction. J Am Coll Cardiol 2001; 38: 1002–1006.
Sarma J, Laan CA, Alam S, Jha A, Fox KA, Dransfield I . Increased platelet binding to circulating monocytes in acute coronary syndromes. Circulation 2002; 105: 2166–2171.
Michelson AD, Barnard MR, Krueger LA, Valeri CR, Furman MI . Circulating monocyte–platelet aggregates are a more sensitive marker of in vivo platelet activation than platelet surface P-selectin: studies in baboons, human coronary intervention, and human acute myocardial infarction. Circulation 2001; 104: 1533–1537.
Knobel H, Jerico C, Montero M, Sorli ML, Velat M, Guelar A et al. Global cardiovascular risk in patients with HIV infection: concordance and differences in estimates according to three risk equations (Framingham, SCORE, and PROCAM). AIDS Patient Care STDS 2007; 21: 452–457.
Edwards-Jackson N, Kerr S, Tieu H, Ananworanich J, Hammer S, Ruxrungtham K et al. Cardiovascular risk assessment in persons with HIV infection in the developing world: comparing three risk equations in a cohort of HIV-infected Thais. HIV Med 2011; 12: 510–515.
Pullinger CR, Aouizerat BE, Gay C, Coggins T, Movsesyan I, Davis H et al. Metabolic abnormalities and coronary heart disease risk in human immunodeficiency virus-infected adults. Metab Syndr Relat Disord 2010; 8: 279–286.
Metcalf Pate KA, Lyons CE, Dorsey JL, Shirk EN, Queen SE, Adams RJ et al. Platelet activation and platelet–monocyte aggregate formation contribute to decreased platelet count during acute simian immunodeficiency virus infection in pig-tailed macaques. J Infect Dis 2013; 208: 874–883.
Singh MV, Davidson DC, Kiebala M, Maggirwar SB . Detection of circulating platelet–monocyte complexes in persons infected with human immunodeficiency virus type-1. J Virol Methods 2012; 181: 170–176.
Davis BH, Zarev PV . Human monocyte CD163 expression inversely correlates with soluble CD163 plasma levels. Cytometry B Clin Cytom 2005; 63: 16–22.
Funderburg NT, Jiang Y, Debanne SM, Storer N, Labbato D, Clagett B et al. Rosuvastatin treatment reduces markers of monocyte activation in HIV infected subjects on antiretroviral therapy. Clin Infect Dis 2014; 58: 588–595.
Alcaide ML, Parmigiani A, Pallikkuth S, Roach M, Freguja R, Della Negra M et al. Immune activation in HIV-infected aging women on antiretrovirals—implications for age-associated comorbidities: a cross-sectional pilot study. PLoS One 2013; 8: e63804.
Krishnan S, Wilson EM, Sheikh V, Rupert A, Mendoza D, Yang J et al. Evidence for innate immune system activation in HIV-1 infected elite controllers. J Infect Dis 2014; 209: 931–939.
Sellam J, Proulle V, Jungel A, Ittah M, Miceli Richard C, Gottenberg JE et al. Increased levels of circulating microparticles in primary Sjogren's syndrome, systemic lupus erythematosus and rheumatoid arthritis and relation with disease activity. Arthritis Res Ther 2009; 11: R156.
Rogacev KS, Cremers B, Zawada AM, Seiler S, Binder N, Ege P et al. CD14++CD16+ monocytes independently predict cardiovascular events: a cohort study of 951 patients referred for elective coronary angiography. J Am Coll Cardiol 2012; 60: 1512–1520.
Bournazos S, Rennie J, Hart SP, Fox KA, Dransfield I . Monocyte functional responsiveness after PSGL-1-mediated platelet adhesion is dependent on platelet activation status. Arterioscler Thromb Vasc Biol 2008; 28: 1491–1498.
Celi A, Pellegrini G, Lorenzet R, de Blasi A, Ready N, Furie BC et al. P-selectin induces the expression of tissue factor on monocytes. Proc Natl Acad Sci USA 1994; 91: 8767–8771.
Weyrich AS, McIntyre TM, McEver RP, Prescott SM, Zimmerman GA . Monocyte tethering by P-selectin regulates monocyte chemotactic protein-1 and tumor necrosis factor-alpha secretion. Signal integration and NF-kappa B translocation. J Clin Invest 1995; 95: 2297–2303.
Davenpeck KL, Brummet ME, Hudson SA, Mayer RJ, Bochner BS . Activation of human leukocytes reduces surface P-selectin glycoprotein ligand-1 (PSGL-1, CD162) and adhesion to P-selectin in vitro. J Immunol 2000; 165: 2764–2772.
Ashman N, Macey MG, Fan SL, Azam U, Yaqoob MM . Increased platelet-monocyte aggregates and cardiovascular disease in end-stage renal failure patients. Nephrol Dial Transplant 2003; 18: 2088–2096.
da Costa Martins PA, van Gils JM, Mol A, Hordijk PL, Zwaginga JJ . Platelet binding to monocytes increases the adhesive properties of monocytes by up-regulating the expression and functionality of beta1 and beta2 integrins. J Leukoc Biol 2006; 79: 499–507.
Yago T, Tsukuda M, Minami M . P-selectin binding promotes the adhesion of monocytes to VCAM-1 under flow conditions. J Immunol 1999; 163: 367–373.
Li G, Sanders JM, Bevard MH, Sun Z, Chumley JW, Galkina EV et al. CD40 ligand promotes Mac-1 expression, leukocyte recruitment, and neointima formation after vascular injury. Am J Pathol 2008; 172: 1141–1152.
Pandrea I, Cornell E, Wilson C, Ribeiro RM, Ma D, Kristoff J et al. Coagulation biomarkers predict disease progression in SIV-infected nonhuman primates. Blood 2012; 120: 1357–1366.
Moller HJ . Soluble CD163. Scand J Clin Lab Invest 2012; 72: 1–13.
Aristoteli LP, Moller HJ, Bailey B, Moestrup SK, Kritharides L . The monocytic lineage specific soluble CD163 is a plasma marker of coronary atherosclerosis. Atherosclerosis 2006; 184: 342–347.
Furman MI, Benoit SE, Barnard MR, Valeri CR, Borbone ML, Becker RC et al. Increased platelet reactivity and circulating monocyte-platelet aggregates in patients with stable coronary artery disease. J Am Coll Cardiol 1998; 31: 352–358.
Li N, Hu H, Lindqvist M, Wikstrom-Jonsson E, Goodall AH, Hjemdahl P . Platelet–leukocyte cross talk in whole blood. Arterioscler Thromb Vasc Biol 2000; 20: 2702–2708.
Acknowledgements
We thank Jenny Hsi for her critical editing of the manuscript. This work was supported by the National Natural Science Foundation of China (31100126, 81271826, 81020108030, 81101281), SKLID Development grants (2011SKLID207, 2012SKLID103), The China National Major Projects for Infectious Diseases Control and Prevention (2012ZX10001008, 2014ZX10001001-002) and the Beijing Natural Science Foundation (7122108).
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Liang, H., Duan, Z., Li, D. et al. Higher levels of circulating monocyte–platelet aggregates are correlated with viremia and increased sCD163 levels in HIV-1 infection. Cell Mol Immunol 12, 435–443 (2015). https://doi.org/10.1038/cmi.2014.66
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DOI: https://doi.org/10.1038/cmi.2014.66
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