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

ABSTRACT: 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.

SUBMITTER: Kim WK

PROVIDER: S-EPMC2858301 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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

Kim Woong-Ki WK Sun Yue Y Do Hien H Autissier Patrick P Halpern Elkan F EF Piatak Michael M Lifson Jeffrey D JD Burdo Tricia H TH McGrath Michael S MS Williams Kenneth K

Journal of leukocyte biology 20091020 4

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 macaq ...[more]

PMID: 19843579

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Project description:Severe traumatic injury has been associated with high susceptibility for the development of secondary complications caused by dysbalanced immune response. As the first line of the cellular immune response, neutrophils and monocytes recruited to the site of tissue damage and/or infection, are divided into three different subsets according to their CD16/CD62L and CD16/CD14 expression, respectively. Their differential functions have not yet been clearly understood. Thus, we evaluated the phenotypic changes of neutrophil and monocyte subsets among their functionality regarding oxidative burst and the phagocytic capacity in severely traumatized patients. Peripheral blood was withdrawn from severely injured trauma patients (TP; n = 15, ISS ≥ 16) within the first 12 h post-trauma and from healthy volunteers (HV; n = 15) and stimulated with fMLP and PMA. CD16dimCD62Lbright (immature), CD16brightCD62Lbright (mature) and CD16brightCD62Ldim (CD62Llow) neutrophil subsets and CD14brightCD16- (classical), CD14brightCD16+ (intermediate) and CD14dimCD16+ (non-classical) monocyte subsets of HV and TP were either directly analyzed by flow cytometry or the examined subsets of HV were sorted first by fluorescence-activated cell sorting and subsequently analyzed. Subset-specific generation of reactive oxygen species (ROS) and of E. coli bioparticle phagocytosis were evaluated. In TP, the counts of immature neutrophils were significantly increased vs. HV. The numbers of mature and CD62Ldim neutrophils remained unchanged but the production of ROS was significantly enhanced in TP vs. HV and the stimulation with fMLP significantly increased the generation of ROS in the mature and CD62Ldim neutrophils of HV. The counts of phagocyting neutrophils did not change but the mean phagocytic capacity showed an increasing trend in TP. In TP, the monocytes shifted toward the intermediate phenotype, whereas the classical and non-classical monocytes became less abundant. ROS generation was significantly increased in all monocyte subsets in TP vs. HV and PMA stimulation significantly increased those level in both, HV and TP. However, the PMA-induced mean ROS generation was significantly lower in intermediate monocytes of TP vs. HV. Sorting of monocyte and neutrophil subsets revealed a significant increase of ROS and decrease of phagocytic capacity vs. whole blood analysis. Neutrophils and monocytes display a phenotypic shift following severe injury. The increased functional abnormalities of certain subsets may contribute to the dysbalanced immune response and attenuate the antimicrobial function and thus, may represent a potential therapeutic target. Further studies on isolated subsets are necessary for evaluation of their physiological role after severe traumatic injury.

Dataset Information

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

Publications

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

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