Monocyte heterogeneity underlying phenotypic changes in monocytes according to SIV disease stage

Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Journal of leukocyte biology (Impact Factor: 4.29). 10/2009; 87(4):557-67. DOI: 10.1189/jlb.0209082
Source: PubMed


Infection by HIV is associated with the expansion of monocytes expressing CD16 antigens, but the significance of this in HIV pathogenesis is largely unknown. In rhesus macaques, at least three subpopulations of blood monocytes were identified based on their expression of CD14 and CD16: CD14(high)CD16(-), CD14(high)CD16(low), and CD14(low)CD16(high). The phenotypes and functions of these subpopulations, including CD16(+) monocytes, were investigated in normal, uninfected rhesus macaques and macaques that were infected with SIV or chimeric SHIV. To assess whether these different monocyte subpopulations expand or contract in AIDS pathogenesis, we conducted a cross-sectional study of 54 SIV- or SHIV-infected macaques and 48 uninfected controls. The absolute numbers of monocyte populations were examined in acutely infected animals, chronically infected animals with no detectable plasma virus RNA, chronically infected animals with detectable plasma virus RNA, and animals that died with AIDS. The absolute numbers of CD14(high)CD16(low) and CD14(low)CD16(high) monocytes were elevated significantly in acutely infected animals and chronically infected animals with detectable plasma virus RNA compared with uninfected controls. Moreover, a significant, positive correlation was evident between the number of CD14(high)CD16(low) or CD14(low)CD16(high) monocytes and plasma viral load in the infected cohort. These data show the dynamic changes of blood monocytes, most notably, CD14(high)CD16(low) monocytes during lentiviral infection, which are specific to disease stage.

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    • "Flow cytometry was performed using the antibodies listed in Table 1, as previously described (Kim et al. 2010). Whole blood and single-cell suspensions from spleens of infected a n i m a l s w e r e s t a i n e d , a n d a n a l y z e d f o r H L A - DR + CD11b + CD14 + CD163 + monocytes/macrophages coexpressing CD206 using FlowJo software (Tree Star, Ashland, OR). "
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    ABSTRACT: We examined the expression of the mannose receptor CD206 by perivascular macrophages (PVM) in normal human and monkey brains and in brains of HIV-infected humans and of monkeys infected with simian immunodeficiency virus (SIV). Depletion of brain PVM in SIV-infected monkeys by intrathecal injection of liposome-encapsulated bisphosphonates eliminated CD206-expressing cells in the brain, confirming their perivascular location and phagocytic capacity. In vivo labeling with bromodeoxyuridine in normal uninfected and SIV-infected macaques in combination with CD206 immunostaining revealed a CD206+-to-CD206- shift within pre-existing PVM during SIV brain infection and neuroinflammation. These findings identify CD206 as a unique marker of human and macaque PVM, and underscore the utility of this marker in studying the origin, turnover and functions of these cells in AIDS.
    Journal of Neuroimmune Pharmacology 08/2014; 9(5). DOI:10.1007/s11481-014-9564-y · 4.11 Impact Factor
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    • "In healthy individuals, 90–95 % of circulating monocytes are only CD14+, while 5–10 % are CD14+ and CD16+ (Ziegler- Heitbrock et al. 1993), which are considered to be more mature. In HIV infected individuals (Nockher et al. 1994; Thieblemont et al. 1995) and SIV infected monkeys (Kim et al. 2010), CD14+CD16+ monocytes were increased in the circulation. Studies showed that these cells were preferentially infected with HIV or SIV when compared to CD14+ CD16-cells (Ancuta et al. 2006; Ellery et al. 2007; Williams et al. 2005; Pulliam et al. 1997). "
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    ABSTRACT: Central nervous system (CNS) complications resulting from HIV infection remain a major public health problem as individuals live longer due to the success of combined antiretroviral therapy (cART). As many as 70 % of HIV infected people have HIV associated neurocognitive disorders (HAND). Many HIV infected individuals abuse drugs, such as cocaine, heroin or methamphetamine, that may be important cofactors in the development of HIV CNS disease. Despite different mechanisms of action, all drugs of abuse increase extracellular dopamine in the CNS. The effects of dopamine on HIV neuropathogenesis are not well understood, and drug induced increases in CNS dopamine may be a common mechanism by which different types of drugs of abuse impact the development of HAND. Monocytes and macrophages are central to HIV infection of the CNS and to HAND. While T cells have not been shown to be a major factor in HIV-associated neuropathogenesis, studies indicate that T cells may play a larger role in the development of HAND in HIV infected drug abusers. Drug induced increases in CNS dopamine may dysregulate functions of, or increase HIV infection in, monocytes, macrophages and T cells in the brain. Thus, characterizing the effects of dopamine on these cells is important for understanding the mechanisms that mediate the development of HAND in drug abusers.
    Journal of Neuroimmune Pharmacology 03/2013; 8(3). DOI:10.1007/s11481-013-9443-y · 4.11 Impact Factor
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    • "However, this work was largely based on SerpinB2-expressing cell lines generated by transfection and selection, a process that can result in clonal bias [1], [13]. Nevertheless, preferential replication of SIV in monkey monocytes expressing SerpinB2 in vivo was observed in a microarray study [14]. Global genomic or RNAi screens have not identified SerpinB2 as an important host protein for HIV replication [15], [16], [17]. "
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    ABSTRACT: SerpinB2, also known as plasminogen activator inhibitor type 2, is a major product of activated monocytes/macrophages and is often strongly induced during infection and inflammation; however, its physiological function remains somewhat elusive. Herein we show that SerpinB2 is induced in peripheral blood mononuclear cells following infection of pigtail macaques with CCR5-utilizing (macrophage-tropic) SIV, but not the rapidly pathogenic CXCR4-utilizing (T cell-tropic) SHIV. To investigate the role of SerpinB2 in lentiviral infections, SerpinB2 mice were infected with EcoHIV, a chimeric HIV in which HIV gp120 has been replaced with gp80 from ecotropic murine leukemia virus. EcoHIV infected SerpinB2 mice produced significantly lower anti- IgG1 antibody titres than infected SerpinB2 mice, and showed slightly delayed clearance of EcoHIV. Analyses of published microarray studies showed significantly higher levels of SerpinB2 mRNA in monocytes from HIV-1 infected patients when compared with uninfected controls, as well as a significant negative correlation between SerpinB2 and T-bet mRNA levels in peripheral blood mononuclear cells. These data illustrate that SerpinB2 can be induced by lentiviral infection and support the emerging notion that a physiological role of SerpinB2 is modulation of Th1/Th2 responses.
    PLoS ONE 02/2013; 8(2):e57343. DOI:10.1371/journal.pone.0057343 · 3.23 Impact Factor
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