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Alveolar macrophages from persons with HIV mount impaired TNF signaling networks to M. tuberculosis infection
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Alveolar macrophages from persons with HIV mount impaired TNF signaling networks to M. tuberculosis infection
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Journal Article
Alveolar macrophages from persons with HIV mount impaired TNF signaling networks to M. tuberculosis infection
2025
Overview
People living with HIV (PLWH) have an increased risk for developing tuberculosis after
M. tuberculosis
infection, despite anti-retroviral therapy (ART). To delineate the underlying mechanisms, we conducted single cell transcriptomics on bronchoalveolar lavage cells from PLWH on ART and HIV uninfected healthy controls infected with
M. tuberculosis
ex vivo. We identify an M1-like proinflammatory alveolar macrophage subset that sequentially acquires TNF signaling capacity in controls but not in PLWH. Cell-cell communication analyses reveal interactions between M1-like macrophages and effector memory T cells within TNF superfamily, chemokine, and costimulatory networks in the airways of controls. These interaction networks were lacking in PLWH infected with
M. tuberculosis
, where anti-inflammatory M2-like alveolar macrophages and T regulatory cells dominated along with dysregulated T cell signatures. Our data support a model in which impaired TNF-TNFR signaling, M2-like alveolar macrophages and aberrant macrophage-T cell crosstalk, lead to ineffective immunity to
M. tuberculosis
in PLWH on ART.
People living with HIV (PLWH) are at high risk of tuberculosis development after Mycobacterium tuberculosis (Mtb) infection. Here the authors compare single cell transcriptomics between BAL cells from PLWH on ART and healthy controls upon ex vivo Mtb infection and find impaired alveolar macrophage (AM) with reduced TNF expression and M1-AM interactions in PLWH.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 49/31
/ 49/91
/ 631/553
/ 96/1
/ Adult
/ Alveoli
/ Bronchoalveolar Lavage Fluid - cytology
/ Bronchus
/ Cell Communication - immunology
/ Female
/ HIV
/ HIV Infections - complications
/ HIV Infections - drug therapy
/ Human immunodeficiency virus
/ Humanities and Social Sciences
/ Humans
/ Lavage
/ Macrophages, Alveolar - immunology
/ Macrophages, Alveolar - metabolism
/ Male
/ Mycobacterium tuberculosis - immunology
/ Networks
/ Science
/ Signal Transduction - immunology
/ Tuberculosis - complications
/ Tumor necrosis factor receptors
