Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Article
  • Published:

Higher levels of circulating monocyte–platelet aggregates are correlated with viremia and increased sCD163 levels in HIV-1 infection

Cellular & Molecular Immunology volume 12, pages 435–443 (2015)Cite this article

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  5. 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.

    Article  CAS  PubMed  Google Scholar 

  6. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ma Y, He B . Recognition of herpes simplex viruses: Toll-like receptors and beyond. J Mol Biol 2014; 426: 1133–1147.

    Article  CAS  PubMed  Google Scholar 

  9. Arpaia N, Barton GM . Toll-like receptors: key players in antiviral immunity. Curr Opin Virol 2011; 1: 447–454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 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.

    Article  CAS  PubMed  Google Scholar 

  11. 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.

    Article  CAS  PubMed  Google Scholar 

  12. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. 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.

    CAS  PubMed  Google Scholar 

  14. van de Veerdonk FL, Netea MG . Diversity: a hallmark of monocyte society. Immunity 2010; 33: 289–291.

    Article  CAS  PubMed  Google Scholar 

  15. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. 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.

    Article  CAS  PubMed  Google Scholar 

  17. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. 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.

    Article  CAS  PubMed  Google Scholar 

  19. 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.

    Article  CAS  PubMed  Google Scholar 

  20. 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.

    Article  PubMed  Google Scholar 

  21. 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.

    Article  CAS  PubMed  Google Scholar 

  22. 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.

    Article  PubMed  Google Scholar 

  23. 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.

    Article  CAS  PubMed  Google Scholar 

  24. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  25. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Davis BH, Zarev PV . Human monocyte CD163 expression inversely correlates with soluble CD163 plasma levels. Cytometry B Clin Cytom 2005; 63: 16–22.

    Article  PubMed  Google Scholar 

  28. 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.

    Article  CAS  PubMed  Google Scholar 

  29. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. 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.

    Article  CAS  PubMed  Google Scholar 

  31. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  32. 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.

    Article  CAS  PubMed  Google Scholar 

  33. 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.

    Article  CAS  PubMed  Google Scholar 

  34. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. 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.

    Article  CAS  PubMed  Google Scholar 

  37. 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.

    Article  CAS  PubMed  Google Scholar 

  38. 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.

    Article  CAS  PubMed  Google Scholar 

  39. 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.

    CAS  PubMed  Google Scholar 

  40. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Moller HJ . Soluble CD163. Scand J Clin Lab Invest 2012; 72: 1–13.

    Article  CAS  PubMed  Google Scholar 

  43. 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.

    Article  CAS  PubMed  Google Scholar 

  44. 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.

    Article  CAS  PubMed  Google Scholar 

  45. 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.

    Article  CAS  PubMed  Google Scholar 

Download references

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).

Author information

Author notes

  1. Dr T Shen, Department of Microbiology, Peking University Health Science Center, Beijing, 100191, China. E-mail: taoshen@bjmu.edu.cn

  2. Dr YM Shao, State Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, China CDC, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing 100026, China. E-mail: yshao08@gmail.com

Authors and Affiliations

  1. State Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, China CDC, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing, China

    Hua Liang, Dan Li, Zheng Wang, Li Ren & Yiming Shao

  2. Department of Microbiology, School of Basic Medical Sciences, Peking University, Beijing, China

    Zhaojun Duan & Tao Shen

  3. Beijing Chaoyang District Center for Disease Control and Prevention, Beijing, China

    Dongliang Li

Authors
  1. Hua Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhaojun Duan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dongliang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zheng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Li Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tao Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yiming Shao
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/cmi.2014.66

Keywords

This article is cited by

Search

Advanced search

Quick links