SIV infection induces accumulation of plasmacytoid dendritic cells in the gut mucosa - PubMed (original) (raw)
SIV infection induces accumulation of plasmacytoid dendritic cells in the gut mucosa
R Keith Reeves et al. J Infect Dis. 2012 Nov.
Abstract
Multiple studies suggest that plasmacytoid dendritic cells (pDCs) are depleted and dysfunctional during human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) infection, but little is known about pDCs in the gut-the primary site of virus replication. Here, we show that during SIV infection, pDCs were reduced 3--fold in the circulation and significantly upregulated the gut-homing marker α4β7, but were increased 4-fold in rectal biopsies of infected compared to naive macaques. These data revise the understanding of pDC immunobiology during SIV infection, indicating that pDCs are not necessarily depleted, but instead may traffic to and accumulate in the gut mucosa.
Figures
Figure 1.
Dendritic cell dynamics in blood and colorectal mucosae of naive and SIV-infected macaques. A, Representative gating strategy for pDCs and mDCs. B, Absolute numbers of pDCs and mDCs in peripheral blood and colorectal biopsies were enumerated using a bead-normalized flow cytometry assay [8]. Black horizontal lines indicate medians. C, MFIs of cell-surface expressed α4β7 on peripheral blood pDCs and mDCs. Bars represent means ± SEM of 9 animals per group. D, Plasma viral loads were correlated with absolute numbers of blood pDCs (upper panel) and cell-surface expression of α4β7 on blood pDCs (middle panel). Mann–Whitney U tests were used for naive-versus-SIV comparisons and Spearman correlation tests were used to assess associations with plasma viral loads. *P < .05; **P < .001.
Figure 2.
Gut mucosal pDCs in situ. A, Representative immunohistochemistry slides of pDCs (stained brown) in colorectal tissue from naive (left panel) and chronically SIV-infected macaques (right panel). B, Quantitative analysis of gut mucosal pDC in naive (n= 3) and SIV-infected (n = 5) macaques. Total CD123+ cells were calculated per mm2 as described in the “Methods” section. The Mann–Whitney U test was used to evaluate significance; *P < .05. C, Immunofluorescent images of CD123 (green) colocalizing with HLA-DR (red) on the surface of pDCs in colorectal tissue. Cell nuclei are counterstained in blue.
Figure 3.
Mucosal pDC function. A, Representative flow cytometry plots showing percentages of colonic pDCs (as gated in Figure 1) expressing intracellular cytokines with and without stimulation. B, Percentages of colonic pDCs from naive and SIV-infected macaques positive for intracellular IFN-α, MIP1-β and TNF-α, without stimulation (media) and with imiquimod added to cultures. Bars represent means ± SEM of 4 animals per group. Unpaired t tests were used for naive-versus-SIV comparisons; *P < .05. Only statistically significant differences are shown.
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