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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Veröffentlicht in:Nature communications Jg. 15; H. 1; S. 8522 - 19
Hauptverfasser: Pisu, Davide, Johnston, Luana, Mattila, Joshua T., Russell, David G.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 02.10.2024
Nature Publishing Group
Nature Portfolio
Schlagworte:
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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
Online-Zugang:Volltext
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Beschreibung
Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-52846-w