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Microbial metabolism disrupts cytokine activity to impact host immune response
File(s)
Author(s)
Marshall, Eleanor KP
Nunes, Catarina
Burbaud, Sophie
Vincent, Crystal M
Munroe, Natalie O
Type
Journal Article
Abstract
Host–pathogen interactions are shaped by the metabolic status of both the host and pathogen. The host must regulate metabolism to fuel the immune response, while the pathogen must extract metabolic resources from the host to enable its own survival. In this study, we focus on the metabolic interactions of Mycobacterium abscessus with Drosophila melanogaster. We identify MAB_1132c as an asparagine transporter required for pathogenicity in M. abscessus. We show that this requirement is specifically associated with damage to the host: flies infected with MAB_1132c knockout bacteria, or with wild-type bacteria grown in asparagine-restricted conditions, are longer lived without showing a significant change in bacterial load. This is associated with a reduction in the host innate immune response, demonstrated by the decreased transcription of antimicrobial peptides as well as a significant reduction in the ability of the infection to disrupt systemic insulin signaling. Much of the increase in host survival during infection with asparagine-limited M. abscessus can be attributed to alterations in unpaired cytokine signaling. This demonstrates that asparagine transport in M. abscessus prior to infection is not required for replicative fitness in vivo but does significantly influence the interaction with the host immune responses.
Date Issued
2024-11-12
Date Acceptance
2024-10-11
Citation
Proceedings of the National Academy of Sciences of USA, 2024, 121 (46)
URI
URL
DOI
ISSN
0027-8424
Publisher
National Academy of Sciences
Journal / Book Title
Proceedings of the National Academy of Sciences of USA
Volume
121
Issue
46
Copyright Statement
Copyright © 2024 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).
License URL
Identifier
https://www.pnas.org/doi/10.1073/pnas.2405719121
Publication Status
Published
Article Number
e2405719121
Date Publish Online
2024-11-08