Loss of anti-inflammatory alveolar macrophages associates with lung inflammation in untreated HIV infection

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Abstract HIV-1 is associated with infectious and noninfectious lung disease, both of which are exacerbated by cigarette smoke. Alveolar macrophages (AMs) are the most prominent immune cell in the alveolar space. These cells play an important role in clearing inhaled pathogens and regulating the inflammatory environment, however, how HIV infection impacts AM function is not well understood, in part due to their autofluorescent properties. The aim of this study was to evaluate the impact of HIV infection on AMs. Utilizing Time of Flight Mass Cytometry (CyTOF) and RNAseq we characterized macrophages from bronchoalveolar lavage (BAL) of HIV-infected and uninfected smokers and nonsmokers. We found that the frequency of alternatively activated AMs, defined by expression of CD163 and CD206, was decreased, while CD163-CCR7+ AM were increased in HIV infection. This phenotype was associated with increased levels of inflammatory cytokines and macrophage activation. While the inflammatory state of macrophages was not impacted by cigarette smoke, other markers such as TLR4 and CXCR4, which are associated with heightened inflammatory response to bacterial products and HIV infection, were altered with smoking. These findings suggest that HIV infection is associated with an increase in pro-inflammatory and depletion of anti-inflammatory AMs, which along with cigarette smoke-induced TLR4 and CXCR4 expression contributes to increased inflammation in the lung. Furthermore, this study demonstrates that CyTOF is a reliable method for immunophenotyping highly autofluorescent cells isolated from the bronchoalveolar lavage of cigarette smokers.