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 cells (BLCs) and peripheral blood mononuclear cells to compare the effect of HIV at the lung mucosal surface and in peripheral blood. The 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 but not in HIV-positive BLCs. DEGs in the HIV-positive BLCs were significantly enriched for infiltration with cytotoxic CD8 + T cells. Higher expression of type 1 interferon transcripts in peripheral CD8 + T cells and representative transcripts and proteins in BLCs-derived 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 functional features of CD8 + T cells infiltrating the lung mucosa during HIV infection may provide novel insights into HIV-induced susceptibility to respiratory pathogens.

Dysregulation of the Immune Environment in the Airways During HIV Infection

“…The presence of HIV in the lung is likely to contribute to immunopathology and immune dysfunction, increasing susceptibility to respiratory diseases. We report a greater number of lymphocytes in HIV-infected airways, as has previously been described as lymphocytic alveolitis, thought to be predominantly made up of cytotoxic CD8+ T cells (24,26,27,37). On its own, lymphocytic alveolitis causes limited pathology (25), but may contribute to the increased prevalence of pulmonary disease during HIV infection.…”

Human Immunodeficiency Virus, Smoking, and Chronic Obstructive Pulmonary Disease: A Case of T Cells Stuck in the Wrong Place?

“…This suggested that HIV-infected individuals had increased BAL CD8 T cells but smoking suppressed this effect. Increased BAL CD8 T cells in HIV-infected individuals have been observed in prior studies including cART naïve HIV-infected subjects (8) and also in HIV-infected individuals started on cART (9). Few studies have focused on HIV-infected individuals on established ART with viral suppression, which was uniquely addressed in this study.…”

Higher Neutrophil-lymphocyte Ratio in TB/HIV Co-infection Compared to Pulmonary Tuberculosis

“…(10) Despite the cavitation that may increase the risk of TB recurrence, human immunodeficiency virus (HIV) coinfection is one of the most important risk factors associated with TB recurrence due to loss or dysfunction of immunity and several other poorly understood mechanisms for immunopathogenesis. (11)(12)(13) TB and HIV has bidirectional impact; TB infection among HIV patient cause slowing CD4 recovery and increasing progression to AIDS; in the other hand HIV infection among TB patient also increase TB disease progression. ( 14) It is estimated that 1.2 million people has died from TB globally, and among these, 17% is HIV infected.…”