The frequency of CD38+ alveolar macrophages correlates with early control of M. tuberculosis in the murine lung

Tuberculosis, caused by Mycobacterium tuberculosis , remains an enduring global health challenge due to the limited efficacy of existing treatments. Although much research has focused on immune failure, the role of host macrophage biology in controlling the disease remains underappreciated. Here we...

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Vydané v:	Nature communications Ročník 15; číslo 1; s. 8522 - 19
Hlavní autori:	Pisu, Davide, Johnston, Luana, Mattila, Joshua T., Russell, David G.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 02.10.2024 Nature Publishing Group Nature Portfolio
Predmet:	38 38/90 38/91 45 631/250/2504/342/1927 631/250/255/1318 631/250/255/1856 631/326/1320 64 64/60 ADP-ribosyl Cyclase 1 - genetics ADP-ribosyl Cyclase 1 - metabolism Alveoli Animal models Animals Bacillus Calmette-Guerin vaccine BCG BCG Vaccine - immunology CD38 antigen Chromatin Disease control Disease Models, Animal Epigenetics Female Gene sequencing Global health Humanities and Social Sciences Immune system Immunization Infections Lung - immunology Lung - microbiology Lung - pathology Macrophages Macrophages, Alveolar - immunology Macrophages, Alveolar - metabolism Macrophages, Alveolar - microbiology Membrane Glycoproteins - immunology Membrane Glycoproteins - metabolism Mice Mice, Inbred C57BL Monocytes multidisciplinary Mycobacterium tuberculosis Mycobacterium tuberculosis - immunology Public health Science Science (multidisciplinary) Single-Cell Analysis Tuberculosis Tuberculosis - immunology Tuberculosis - microbiology Tuberculosis, Pulmonary - immunology Tuberculosis, Pulmonary - microbiology Tuberculosis, Pulmonary - pathology Vaccines
ISSN:	2041-1723, 2041-1723
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Shrnutí:	Tuberculosis, caused by Mycobacterium tuberculosis , remains an enduring global health challenge due to the limited efficacy of existing treatments. Although much research has focused on immune failure, the role of host macrophage biology in controlling the disease remains underappreciated. Here we show, through multi-modal single-cell RNA sequencing in a murine model, that different alveolar macrophage subsets play distinct roles in either advancing or controlling the disease. Initially, alveolar macrophages that are negative for the CD38 marker are the main infected population. As the infection progresses, CD38 + monocyte-derived and tissue-resident alveolar macrophages emerge as significant controllers of bacterial growth. These macrophages display a unique chromatin organization pre-infection, indicative of epigenetic priming for pro-inflammatory responses. Moreover, intranasal BCG immunization increases the numbers of CD38 + macrophages, enhancing their capability to restrict Mycobacterium tuberculosis growth. Our findings highlight the dynamic roles of alveolar macrophages in tuberculosis and open pathways for improved vaccines and therapies. Mycobacterium tuberculosis infection remains a global health crisis. Here researchers characterise the alveolar macrophage subsets in a murine model of BCG vaccination in mice and link increases of CD38+ macrophages with restriction of bacterial growth.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-024-52846-w