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. 2018 Apr 6:2:105.
doi: 10.12688/wellcomeopenres.12869.3. eCollection 2017.

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

Andrew Mwale  1 , Annemarie Hummel  1 , Leonard Mvaya  1 , Raphael Kamng'ona  1 , Elizabeth Chimbayo  1 , Joseph Phiri  1 , Rose Malamba  1 , Anstead Kankwatira  1 , Henry C Mwandumba  1   2 , Kondwani C Jambo  1   2
Affiliations

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

Andrew Mwale et al. Wellcome Open Res. .

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.

Keywords: B cell; BAL; CD4 T cell; CD8 T cell; HIV; adult; alveolitis; gamma-delta T cells.

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Conflict of interest statement

Competing interests: No competing interests were disclosed.

Figures

Figure 1.
Figure 1.. Representative flow cytometry plots for characterising lymphocytes in BAL fluid from HIV-uninfected adult.
BAL cells were stained with fluorochrome-conjugated antibodies.
Figure 2.
Figure 2.. Proportions and numbers of CD4 + T cells, CD8 + T cells and CD19 + B cells in BAL fluid from ART-naïve HIV-infected compared to HIV-uninfected individuals.
BAL cells were stained with fluorochrome-conjugated antibodies. A) Proportion of lymphocytes in BAL fluid. B) Numbers of lymphocytes in BAL fluid. C) Proportion of CD4 + and CD8 + T cells in BAL fluid. D) Numbers of CD4 + and CD8 + T cells in BAL fluid. E) Proportion of B cells in BAL fluid. F) Numbers of CD19 + B cells in BAL fluid. The horizontal bars represent median and 95% confidence intervals. Data were analyzed using Mann Whitney U test. (HIV-, n=20; HIV+ ART-, n=17).
Figure 3.
Figure 3.. Proportions and numbers of γδ T cells and NK cells in BAL fluid from ART-naïve HIV-infected compared to HIV-uninfected individuals.
BAL cells were stained with fluorochrome-conjugated antibodies. A) Proportion of γδ T cell subsets in BAL fluid. B) Numbers of γδ T cell subsets in BAL fluid. C) Proportion of NK cell subsets in BAL fluid. D) Numbers of NK cell subsets in BAL fluid. The horizontal bars represent median and 95% confidence intervals. Data were analyzed using Mann Whitney U test. (HIV-, n=20; HIV+ ART-, n=17).
Figure 4.
Figure 4.. Representative flow cytometry plots for characterising myeloid cells in BAL fluid from an HIV-uninfected adult.
BAL cells were stained with fluorochrome-conjugated antibodies.
Figure 5.
Figure 5.. Proportions and numbers of monocyte subsets in BAL fluid and peripheral blood from ART-naïve HIV-infected compared to HIV-uninfected individuals.
BAL cells and PBMCs were stained with fluorochrome-conjugated antibodies. A) Flow cytometry representative plot of stained BAL sample from an HIV-uninfected control. B) Flow cytometry representative plot of stained peripheral blood sample from an HIV-uninfected control. C) Proportion of monocytes subsets in BAL fluid. D) Proportion of monocyte subsets in peripheral blood. E) Numbers of monocytes subsets in BAL fluid. F) Numbers of monocyte subsets in peripheral blood.The horizontal bars represent median and 95% confidence intervals. Data were analyzed using Mann Whitney U test. (BAL fluid, HIV-, n = 20; HIV+ ART-, n = 17; PBMC, HIV-, n=16; HIV+ ART-, n=14).
Figure 6.
Figure 6.. Proportions and numbers of alveolar macrophages, neutrophils and dendritic cells in BAL fluid from ART-naïve HIV-infected compared to HIV-uninfected individuals.
BAL cells were stained with fluorochrome-conjugated antibodies. A) Proportion of alveoalar macrophages and neutrophils in BAL fluid. B) Numbers of alveoalar macrophages and neutrophils in BAL fluid. C) Proportion of dendritic cell subsets in BAL fluid. D) Numbers of dendritic cell subsets in BAL fluid. The horizontal bars represent median and 95% confidence intervals. Data were analyzed using Mann Whitney U test. (HIV-, n = 20; HIV+ ART-, n = 17).
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