Small alveolar macrophages are infected preferentially by HIV and exhibit impaired phagocytic function.
HIV-1-infected persons are at higher risk of lower respiratory tract infections than HIV-1-uninfected individuals. This suggests strongly that HIV-infected persons have specific impairment of pulmonary immune responses, but current understanding of how HIV alters pulmonary immunity is incomplete. Alveolar macrophages (AMs), comprising small and large macrophages, are major effectors of innate immunity in the lung. We postulated that HIV-1 impairs pulmonary innate immunity through impairment of AM physiological functions. AMs were obtained by bronchoalveolar lavage from healthy, asymptomatic, antiretroviral therapy-naive HIV-1-infected and HIV-1-uninfected adults. We used novel assays to detect in vivo HIV-infected AMs and to assess AM functions based on the HIV infection status of individual cells. We show that HIV has differential effects on key AM physiological functions, whereby small AMs are infected preferentially by the virus, resulting in selective impairment of phagocytic function. In contrast, HIV has a more generalized effect on AM proteolysis, which does not require direct viral infection. These findings provide new insights into how HIV alters pulmonary innate immunity and the phenotype of AMs that harbors the virus. They underscore the need to clear this HIV reservoir to improve pulmonary immunity and reduce the high incidence of lower respiratory tract infections in HIV-1-infected individuals.
1] Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi [2] Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
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Jambo
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.
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DH
Banda
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.
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AM
Kankwatira
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
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Sukumar
Department of Medicine, College of Medicine, Blantyre, Malawi.
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TJ
Allain
1] Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi [2] Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK [3] Department of Medicine, College of Medicine, Blantyre, Malawi.
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Heyderman
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
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Russell
1] Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi [2] Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK [3] Department of Medicine, College of Medicine, Blantyre, Malawi.
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Mwandumba
D000328:Adult; D018893:Bronchoalveolar Lavage; D048429:Cell Size; D005260:Female; D005434:Flow Cytometry; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D010587:Phagocytosis / Q000276:immunology*; D055815:Young Adult