Autophagy restricts Mycobacterium tuberculosis during acute infection in mice.


Journal

Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869

Informations de publication

Date de publication:
05 2023
Historique:
received: 03 09 2021
accepted: 03 03 2023
medline: 8 5 2023
pubmed: 11 4 2023
entrez: 10 4 2023
Statut: ppublish

Résumé

Whether or not autophagy has a role in defence against Mycobacterium tuberculosis infection remains unresolved. Previously, conditional knockdown of the core autophagy component ATG5 in myeloid cells was reported to confer extreme susceptibility to M. tuberculosis in mice, whereas depletion of other autophagy factors had no effect on infection. We show that doubling cre gene dosage to more robustly deplete ATG16L1 or ATG7 resulted in increased M. tuberculosis growth and host susceptibility in mice, although ATG5-depleted mice are more sensitive than ATG16L1- or ATG7-depleted mice. We imaged individual macrophages infected with M. tuberculosis and identified a shift from apoptosis to rapid necrosis in autophagy-depleted cells. This effect was dependent on phagosome permeabilization by M. tuberculosis. We monitored infected cells by electron microscopy, showing that autophagy protects the host macrophage by partially reducing mycobacterial access to the cytosol. We conclude that autophagy has an important role in defence against M. tuberculosis in mammals.

Identifiants

pubmed: 37037941
doi: 10.1038/s41564-023-01354-6
pii: 10.1038/s41564-023-01354-6
pmc: PMC11027733
mid: NIHMS1981926
doi:

Substances chimiques

Autophagy-Related Protein 5 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

819-832

Subventions

Organisme : NIAID NIH HHS
ID : P01 AI063302
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI135990
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI162583
Pays : United States
Organisme : NIH HHS
ID : S10 OD010786
Pays : United States

Commentaires et corrections

Type : CommentIn
Type : ErratumIn

Informations de copyright

© 2023. The Author(s), under exclusive licence to Springer Nature Limited.

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Auteurs

Guillaume R Golovkine (GR)

Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Evotec, Toulouse, France.

Allison W Roberts (AW)

Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.

Huntly M Morrison (HM)

Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.

Rafael Rivera-Lugo (R)

Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.

Rita M McCall (RM)

Department of Plant & Microbial Biology, University of California, Berkeley, CA, USA.

Hannah Nilsson (H)

Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.

Nicholas E Garelis (NE)

Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.

Teresa Repasy (T)

Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Bio-Rad Laboratories, Seattle, WA, USA.

Michael Cronce (M)

Department of Bioengineering, University of California, Berkeley, CA, USA.
UC Berkeley-UCSF Graduate program in Bioengineering, Berkeley, CA, USA.

Jonathan Budzik (J)

Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Department of Medicine, University of California, San Francisco, CA, USA.
Department of Medicine, University of California, San Francisco, CA, USA.

Erik Van Dis (E)

Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Department of Immunology, University of Washington School of Medicine, Seattle, WA, USA.

Lauren M Popov (LM)

Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Novome Biotechnologies, San Francisco, CA, USA.

Gabriel Mitchell (G)

Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Open Innovation @ NITD, Novartis Institute for Tropical Diseases, Emeryville, CA, USA.

Reena Zalpuri (R)

Electron Microscope Laboratory, University of California, Berkeley, CA, USA.

Danielle Jorgens (D)

Electron Microscope Laboratory, University of California, Berkeley, CA, USA.

Jeffery S Cox (JS)

Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA. jeff.cox@berkeley.edu.

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