B cell, CD8 + T cell and gamma delta T cell infiltration alters alveolar immune cell homeostasis in HIV-infected Malawian adults

Abstract

Background: HIV infection is associated with increased risk to lower respiratory tract infections (LRTI). However, the impact of HIV infection on immune cell populations in the lung is not well defined. We sought to comprehensively characterise the impact of HIV infection on immune cell populations in the lung. Methods: Twenty HIV-uninfected controls and 17 HIV-1 infected ART-naïve adults were recruited from Queen Elizabeth Central Hospital, Malawi. Immunophenotyping of lymphocyte and myeloid cell populations was done on bronchoalveolar lavage fluid and peripheral blood cells. Results: We found that the numbers of CD8 + T cells, B cells and gamma delta T cells were higher in BAL fluid of HIV-infected adults compared to HIV-uninfected controls (all p<0.05). In contrast, there was no difference in the numbers of alveolar CD4 + T cells in HIV-infected adults compared to HIV-uninfected controls (p=0.7065). Intermediate monocytes were the predominant monocyte subset in BAL fluid (HIV-, 63%; HIV+ 81%), while the numbers of classical monocytes was lower in HIV-infected individuals compared to HIV-uninfected adults (1 × 10 5 vs. 2.8 × 10 5 cells/100ml of BAL fluid, p=0.0001). The proportions of alveolar macrophages and myeloid dendritic cells was lower in HIV-infected adults compared to HIV-uninfected controls (all p<0.05). Conclusions: Chronic HIV infection is associated with broad alteration of immune cell populations in the lung, but does not lead to massive depletion of alveolar CD4 + T cells. Disruption of alveolar immune cell homeostasis likely explains in part the susceptibility for LRTIs in HIV-infected adults.

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

“…We also observed contribution by inhibitory/exhaustion markers (PD-1 ( PDCD1 ) and LAG-3 ( LAG3 )) in the enrichment of this GO term. Further observation of B-cell transcripts ( CD19, CD79A and CD79B ) suggests that HIV also induces infiltration of the bronchoalveolar compartment by other lymphocytes as previously reported 15 (Figure 3C).…”

“…The infiltration of the bronchoalveolar compartment of HIV-positive patients with CD8 + T cells has been reported in previous studies. However, there is limited information on its functional nature 15, 18 . Using both flow cytometry and whole compartment and CD8 + T cell specific RNA-seq, we show that the HIV-induced CD8 + T-cell infiltrate is associated with higher expression of effector molecules such as granzymes, perforin and interferon gamma, suggesting a cytolytic and inflammatory profile.…”

HIV-1 and SIV Infection Are Associated with Early Loss of Lung Interstitial CD4+ T Cells and Dissemination of Pulmonary Tuberculosis

“…Here we describe early severe depletion of lung interstitial CD4+ T cells in vitro and in vivo , induced by HIV-1 in human cells and by SIV in NHPs. Previously, human studies of lung CD4+ T cells in HIV-infected subjects have used BAL as a surrogate for interstitial tissue cells and have suggested minimal or no depletion of CD4+ T cells in this compartment (Brenchley et al, 2008; Bunjun et al, 2017; Mwale et al, 2018). A study in NHPs reported transient BAL CD4+ T cell depletion that was rapidly reversed by infiltrating CD4+ T cells with increased anti-viral resistance (Verhoeven et al, 2014).…”

γδ T‐cell responses during HIV infection and antiretroviral therapy

“…Tuberculosis is currently the leading cause of death among HIV-infected individuals, and evidence suggests that active TB and HIV infection have additive effects on peripheral Vd2 depletion 89 and dysfunction. 91 However, the possible impact of HIV infection on Vd2 responses to Mycobacterium has been clearly demonstrated in NHP models. Only a single study has reported BAL cd T-cell numbers in healthy and HIV-infected participants where there was a significant increase in total cd cells during HIV infection, but the delta chain usage was not determined.…”

“…Only a single study has reported BAL cd T-cell numbers in healthy and HIV-infected participants where there was a significant increase in total cd cells during HIV infection, but the delta chain usage was not determined. 91 However, the possible impact of HIV infection on Vd2 responses to Mycobacterium has been clearly demonstrated in NHP models. Na€ ıve macaques are able to induce robust primary and recall Vd2 responses to BCG vaccination in the periphery and lung, while SIV-infected macaques showed no response to BCG in either site.…”