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

Article (PDF Available)inJournal of leukocyte biology 87(4):557-67 · October 2009with30 Reads
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.
    • "The significant functional overlap of intermediate monocytes with classical and non-classical monocytes lends credence to the present hypothesis that CD14 ++ CD16 − monocytes arise from the bone marrow and give rise to CD14 ++ CD16 + and CD14 + CD16 ++ monocytes [4,13,24] . CD14 ++ CD16 − monocytes primarily produce monocyte chemotactic protein-1 (MCP-1/CCL2) and express its cognate receptor CCR2, as do intermediate monocytes [14,22]. CCR2 is critical for monocyte emigration from the bone marrow and monocyte homing2526272829 . "
    [Show abstract] [Hide abstract] ABSTRACT: Monocytes are primitive hematopoietic cells that primarily arise from the bone marrow, circulate in the peripheral blood and give rise to differentiated macrophages. Over the past two decades, considerable attention to monocyte diversity and macrophage polarization has provided contextual clues into the role of myelomonocytic derivatives in human disease. Until recently, human monocytes were subdivided based on expression of the surface marker CD16. "Classical" monocytes express surface markers denoted as CD14(++)CD16(-) and account for greater than 70% of total monocyte count, while "non-classical" monocytes express the CD16 antigen with low CD14 expression (CD14(+)CD16(++)). However, recognition of an intermediate population identified as CD14(++)CD16(+) supports the new paradigm that monocytes are a true heterogeneous population and careful identification of specific subpopulations is necessary for understanding monocyte function in human disease. Comparative studies of monocytes in mice have yielded more dichotomous results based on expression of the Ly6C antigen. In this review, we will discuss the use of monocyte subpopulations as biomarkers of human disease and summarize correlative studies in mice that may yield significant insight into the contribution of each subset to disease pathogenesis.
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    • "In addition, the intermediate and/ or non-classical PBMs produce high levels of the inflammatory cytokines (e.g., TNF-α and IL-1) in response to a wide variety of pattern receptor ligands [21][22][23], whereas the classical PBMs are the main producers of antiinflammatory IL-10 [22, 23, 24]. This is also concordant with the reports that CD16 + PBMs are considerably expanded under various inflammation and infectious condi- tions [16,[25][26][27][28]. Fig. 1The origin and differentiation of peripheral blood monocytes. "
    [Show abstract] [Hide abstract] ABSTRACT: Peripheral blood monocytes (PBMs) are an important source of precursors of osteoclasts, the bone-resorbing cells and the cytokines produced by PBMs that have profound effects on osteoclast differentiation, activation, and apoptosis. So PBMs represent a highly valuable and unique working cell model for bone-related study. Finding an appropriate working cell model for clinical and (epi-)genomic studies of human skeletal disorders is a challenge. Peripheral blood monocytes (PBMs) can give rise to osteoclasts, the bone-resorbing cells. Particularly, PBMs provide the sole source of osteoclast precursors for adult peripheral skeleton where the bone marrow is normally hematopoietically inactive. PBMs can secrete potent pro- and anti-inflammatory cytokines, which are important for osteoclast differentiation, activation, and apoptosis. Reduced production of PBM cytokines represents a major mechanism for the inhibitory effects of sex hormones on osteoclastogenesis and bone resorption. Abnormalities in PBMs have been linked to various skeletal disorders/traits, strongly supporting for the biological relevance of PBMs with bone metabolism and disorders. Here, we briefly review the origin and further differentiation of PBMs. In particular, we discuss the close relationship between PBMs and osteoclasts, and highlight the utility of PBMs in study the pathophysiological mechanisms underlying various skeletal disorders.
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    • "In acute infection, there was an increase in CD14 ++ CD16 + and CD14 + CD16 ++ monocytes, while CD14 ++ CD16 − monocytes decreased two weeks after infection [53]. Similarly, there was increase in CD14 ++ CD16 + and CD14 + CD16 ++ monocytes subsets in rhesus macaques with chronic infection and high viral load [53,54]. Moreover, in HIV-1 infected patients, the preferential expansion of CD14 ++ CD16 + monocyte subset is associated with increased intracellular level of CCL2 [55]. "
    [Show abstract] [Hide abstract] ABSTRACT: Human immunodeficiency virus type 1 (HIV-1) establishes latency in resting memory CD4+ T cells and cells of myeloid lineage. In contrast to the T cells, cells of myeloid lineage are resistant to the HIV-1 induced cytopathic effect. Cells of myeloid lineage including macrophages are present in anatomical sanctuaries making them a difficult drug target. In addition, the long life span of macrophages as compared to the CD4+ T cells make them important viral reservoirs in infected individuals especially in the late stage of viral infection where CD4+ T cells are largely depleted. In the past decade, HIV-1 persistence in resting CD4+ T cells has gained considerable attention. It is currently believed that rebound viremia following cessation of combination anti-retroviral therapy (cART) originates from this source. However, the clinical relevance of this reservoir has been questioned. It is suggested that the resting CD4+ T cells are only one source of residual viremia and other viral reservoirs such as tissue macrophages should be seriously considered. In the present review we will discuss how macrophages contribute to the development of long-lived latent reservoirs and how macrophages can be used as a therapeutic target in eradicating latent reservoir.
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