Abstract
Uncontrolled HIV infection progresses to the depletion of systemic and mucosal CD4 and AIDS. Early HIV infection may be associated with increases in the concentration of MIP-3α in the blood and gut fluids. MIP-3α/CCL20 is the only chemokine known to interact with CCR6 receptors which are expressed on immature dendritic cells and both effector and memory CD8+ and CD4+ T cells. The role and prognostic value of blood levels of MIP-3α in HIV-infected individuals has yet to be described. We determined the serum levels of MIP-3α, and IFN-γ, in 167 HIV-1-infected and 27 HIV-1-uninfected men participating in the Multicenter AIDS Cohort Study (MACS). The blood biomarkers were measured using enzyme-linked immunosorbent assays (ELISA) and the cell phenotypes using flow cytometry. Median serum levels of MIP-3α in HIV-1-infected and uninfected men was significantly different (p<0.0001) and were 21.3 pg/mL and 6.4 pg/mL respectively. The HIV-1-infected men with CD4+ T cell count <200 cells/μL showed the highest median serum MIP-3α (23.1 pg/mL). Serum levels of MIP-3α in HIV-1 infected (n=167) were negatively correlated with absolute number of CD4+ T cell (p=0.01) and were positively correlated with CD38 molecules on CD8+ T cells (p=0.0002) and with serum levels of IFN-γ (0.006). Serum levels of MIP-3α concomitantly increase with plasma levels of IFN-γ, CD38 expression on CD8+ T cells, and decreased of absolute CD4+ T cells in HIV-1-infected men. A higher blood level of MIP-3α may be representation of locally high level of MIP-3α and more recruitment of immature dendritic cell at site of infection. Involvement of CCR6/CCL20 axis and epithelial cells at the recto-colonel level may enhance sexual transmission of HIV-1 in MSM and may be useful as a prognostic marker in HIV-1-infection and AIDS.
Highlights
Chemokines are small polypeptides (90-130 amino acids) that regulate cellular activation, chemotaxis, leukocyte trafficking, and cellular adhesion
Specimens Serum samples from HIV-1-infected and HIV-1-uninfected men participating in the Multicenter AIDS Cohort Study (MACS) of the Natural History of AIDS at UCLA were selected based on the absolute CD4+ T cell counts (400 cells/μl) [38]
Concentrations of CCL20/MIP-3α were significantly higher in HIV-1-infected men with CD4+ T cell counts 400 cells/μL (p=0.0052)
Summary
Chemokines are small polypeptides (90-130 amino acids) that regulate cellular activation, chemotaxis, leukocyte trafficking, and cellular adhesion. There are approximately 40-50 currently known human chemokines that are divided into two subfamilies (CXC and CC) with more than 20 receptors [1,2,3,4]. MIP-3α is the only chemokine that has high specificity for the chemokine receptor, CCR6 [10,11,12,13], which is expressed on several human cell types implicated in HIV infection, including immature dendritic cells (iDCs) [14], effector/memory CD8+ and CD4+ T cells [15,16], and interleukin-17 (IL-17) producing T cells (TH17). CCL20/MIP-3α is responsible for the chemo-attraction of iDCs, effector/memory B cells and T cells. CCL20/MIP-3α has been shown to be chemotactic for CD11b+ myeloid DCs in the Peyer's patch, and is involved in the regulation of humoral immunity and lymphocyte homeostasis
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