Abstract
We have previously demonstrated the critical role of C-C chemokine CCL2 in HIV-1 pathogenesis, and circulating monocytes as the major source of CCL2. Since the functional aspect of monocyte subsets in context to CCL2 production is unclear, we investigated the frequency and production of CCL2 by circulating monocyte subsets in a cohort of HIV- therapy naïve patients. A cohort of HIV-infected therapy naïve patients (n = 9) and healthy controls (n = 6) were recruited for this study. To examine monocyte subset frequency and CCL2 production, we performed surface and intra-cellular staining of freshly isolated peripheral blood mononuclear cells (PBMC) and subjected to flow cytometry. A preferential expansion of CD14+CD16+ monocyte subset, coupled with increased intracellular production of CCL2 was observed in HIV-1 patients compared to healthy controls. Interestingly this phenotype was mostly restricted to CD14+CD16+ monocyte subsets. This study identifies pro-inflammatory CCL2 producing CD14+CD16+ monocyte subset that expands selectively in HIV-1 infection and could potentially participate in causing immuno-pathology.
References
Ansari AW, Heiken H, Meyer-Olson D, Schmidt RE. CCL2: a potential prognostic marker and target of anti-inflammatory strategy in HIV/AIDS pathogenesis. Eur J Immunol. 2011;41:3412–8.
Ansari AW, Bhatnagar N, Dittrich-Breiholz O, Kracht M, Schmidt RE, Heiken H. Host chemokine (C-C motif) ligand-2 (CCL2) is differentially regulated in HIV type 1 (HIV-1)-infected individuals. Int Immunol. 2006;18:1443–51.
Ansari AW, Schmidt RE, Heiken H. Prednisolone mediated suppression of HIV-1 viral load strongly correlates with C-C chemokine CCL2: In vivo and in vitro findings. Clin Immunol. 2007;125:1–4.
Cinque P, Vago L, Mengozzi M, Torri V, Ceresa D, Vicenzi E, et al. Elevated cerebrospinal fluid levels of monocyte chemotactic protein-1 correlate with HIV-1 encephalitis and local viral replication. AIDS. 1998;12:1327–32.
Berger EA, Doms RW, Fenyo EM, Korber BT, Littman DR, Moore JP, et al. A new classification for HIV-1. Nature. 1998;391:240.
Gonzalez E, Rovin BH, Sen L, Cooke G, Dhanda R, Mummidi S, et al. HIV-1 infection and AIDS dementia are influenced by a mutant MCP-1 allele linked to increased monocyte infiltration of tissues and MCP-1 levels. Proc Natl Acad Sci U S A. 2002;99:13795–800.
Ansari AW, Heiken H, Moenkemeyer M, Schmidt RE. Dichotomous effects of C-C chemokines in HIV-1 pathogenesis. Immunol Lett. 2007;110:1–5.
Campbell GR, Watkins JD, Singh KK, Loret EP, Spector SA. Human immunodeficiency virus type 1 subtype C Tat fails to induce intracellular calcium flux and induces reduced tumor necrosis factor production from monocytes. J Virol. 2007;81:5919–28.
Gu L, Tseng S, Horner RM, Tam C, Loda M, Rollins BJ. Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1. Nature. 2000;404:407–11.
Jourdan P, Abbal C, Noraz N, Hori T, Uchiyama T, Vendrell JP, et al. IL-4 induces functional cell-surface expression of CXCR4 on human T cells. J Immunol. 1998;160:4153–7.
Fantuzzi L, Spadaro F, Vallanti G, Canini I, Ramoni C, Vicenzi E, et al. Endogenous CCL2 (monocyte chemotactic protein-1) modulates human immunodeficiency virus type-1 replication and affects cytoskeleton organization in human monocyte-derived macrophages. Blood. 2003;102:2334–7.
Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol. 2005;5:953–64.
Wong KL, Tai JJ, Wong WC, Han H, Sem X, Yeap WH, et al. Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets. Blood. 2012;118:e16–31.
Strauss-Ayali D, Conrad SM, Mosser DM. Monocyte subpopulations and their differentiation patterns during infection. J Leukoc Biol. 2007;82:244–52.
Ziegler-Heitbrock HW, Strobel M, Kieper D, Fingerle G, Schlunck T, Petersmann I, et al. Differential expression of cytokines in human blood monocyte subpopulations. Blood. 1992;79:503–11.
Passlick B, Flieger D, Ziegler-Heitbrock HW. Identification and characterization of a novel monocyte subpopulation in human peripheral blood. Blood. 1989;74:2527–34.
Wong KL, Yeap WH, Tai JJ, Ong SM, Dang TM, Wong SC. The three human monocyte subsets: implications for health and disease. Immunol Res. 2012;53:41–57.
Ellery PJ, Tippett E, Chiu YL, Paukovics G, Cameron PU, Solomon A, et al. The CD16+ monocyte subset is more permissive to infection and preferentially harbors HIV-1 in vivo. J Immunol. 2007;178:6581–9.
Naif HM, Li S, Alali M, Sloane A, Wu L, Kelly M, et al. CCR5 expression correlates with susceptibility of maturing monocytes to human immunodeficiency virus type 1 infection. J Virol. 1998;72:830–6.
Zhu T. HIV-1 in peripheral blood monocytes: an underrated viral source. J Antimicrob Chemother. 2002;50:309–11.
Ancuta P, Autissier P, Wurcel A, Zaman T, Stone D, Gabuzda D. CD16+ monocyte-derived macrophages activate resting T cells for HIV infection by producing CCR3 and CCR4 ligands. J Immunol. 2006;176:5760–71.
Gama L, Shirk EN, Russell JN, Carvalho KI, Li M, Queen SE, et al. Expansion of a subset of CD14highCD16negCCR2low/neg monocytes functionally similar to myeloid-derived suppressor cells during SIV and HIV infection. J Leukoc Biol. 2012;91:803–16.
Alkhatib G, Combadiere C, Broder CC, Feng Y, Kennedy PE, Murphy PM, et al. CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science. 1996;272:1955–8.
Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P. Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science. 1995;270:1811–5.
Han J, Wang B, Han N, Zhao Y, Song C, Feng X, et al. CD14(high)CD16(+) rather than CD14(low)CD16(+) monocytes correlate with disease progression in chronic HIV-infected patients. J Acquir Immune Defic Syndr. 2009;52:553–9.
Zimmermann HW, Seidler S, Nattermann J, Gassler N, Hellerbrand C, Zernecke A, et al. Functional contribution of elevated circulating and hepatic non-classical CD14CD16 monocytes to inflammation and human liver fibrosis. PLoS One. 2010;5:e11049.
Zhang JY, Zou ZS, Huang A, Zhang Z, Fu JL, Xu XS, et al. Hyper-activated pro-inflammatory CD16 monocytes correlate with the severity of liver injury and fibrosis in patients with chronic hepatitis B. PLoS One. 2011;6:e17484.
Tuyama AC, Hong F, Saiman Y, Wang C, Ozkok D, Mosoian A, et al. Human immunodeficiency virus (HIV)-1 infects human hepatic stellate cells and promotes collagen I and monocyte chemoattractant protein-1 expression: implications for the pathogenesis of HIV/hepatitis C virus-induced liver fibrosis. Hepatology. 2012;52:612–22.
Acknowledgements
We are indebt to HIV-1 patients and healthy volunteers who participated in this study. We thank members of the routine HIV labor for excellent assistance. Also, we extend our thanks to Nupur Bhatnagar and Fareed Ahmed for their help in PBMC isolation.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ansari, A.W., Meyer-Olson, D. & Schmidt, R.E. Selective Expansion of Pro-inflammatory Chemokine CCL2-Loaded CD14+CD16+ Monocytes Subset in HIV-Infected Therapy Naïve Individuals. J Clin Immunol 33, 302–306 (2013). https://doi.org/10.1007/s10875-012-9790-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10875-012-9790-0