Contrasting inflammatory signatures in peripheral blood and bronchoalveolar cells reveal compartment-specific effects of HIV infection.

Abstract

The mechanisms by which HIV increases susceptibility to tuberculosis and other respiratory infections are incompletely understood. We used transcriptomics of paired whole bronchoalveolar lavage (BAL) fluid and peripheral blood mononuclear cells to compare the effect of HIV at the lung mucosal surface and in the peripheral blood. The large majority of HIV-induced differentially expressed genes (DEGs) were specific to either the peripheral or lung mucosa compartments (1,307/1,404, 93%). Type I interferon signaling was the dominant signature of DEGs in HIV-positive blood with a less dominant and qualitatively distinct type I interferon gene set expression pattern in HIV-positive BAL. DEGs in the HIV-positive BAL were significantly enriched for infiltration with cytotoxic CD8+ T cells. Higher expression of representative transcripts and proteins in BAL CD8+ T cells during HIV infection, including IFNG (IFN-{gamma}), GZMB (Granzyme B) and PDCD1 (PD-1), was confirmed by cell-subset specific transcriptional analysis and flow cytometry. Thus, we report that a whole transcriptomic approach revealed qualitatively distinct effects of HIV in blood and bronchoalveolar compartments. Further work exploring the impact of distinct type I interferon programs and CD8+ T cells infiltration of the lung mucosa during HIV infection may provide novel insights into HIV-induced susceptibility to respiratory pathogens.