HIV Infection Is Associated with Loss of Anti-Inflammatory Alveolar Macrophages

Autor: Thomas B. Campbell, Shaikh M. Atif, Brent E. Palmer, James C. Lavelle, Andrew P. Fontenot, Carsten Görg, Eric C. Logue, Janet C Siebert, Homer L. Twigg, Suzanne Fiorillo, Charles Preston Neff
Rok vydání: 2020
Předmět:
Zdroj: J Immunol
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.2000361
Popis: HIV type 1 is associated with pulmonary dysfunction that is exacerbated by cigarette smoke. Alveolar macrophages (AM) 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 phenotype and function is not well understood, in part because of their autofluorescence and the absence of well-defined surface markers. The main aim of this study was to evaluate the impact of HIV infection on human AM and to compare the effect of smoking on their phenotype and function. Time-of-flight mass cytometry and RNA sequencing were used to characterize macrophages from human bronchoalveolar lavage of HIV-infected and -uninfected smokers and nonsmokers. We found that the frequency of CD163+ anti-inflammatory AM was decreased, whereas CD163−CCR7+ proinflammatory AM were increased in HIV infection. HIV-mediated proinflammatory polarization was associated with increased levels of inflammatory cytokines and macrophage activation. Conversely, smoking heightened the inflammatory response evident by change in the expression of CXCR4 and TLR4. Altogether, these findings suggest that HIV infection, along with cigarette smoke, favors a proinflammatory macrophage phenotype associated with enhanced expression of inflammatory molecules. Further, this study highlights time-of-flight mass cytometry as a reliable method for immunophenotyping the highly autofluorescent cells present in the bronchoalveolar lavage of cigarette smokers.
Databáze: OpenAIRE