Klebsiella pneumoniae induces host metabolic stress that promotes tolerance to pulmonary infection.
Klebsiella pneumoniae
M2 macrophages
MDSCs
bacterial adaptation
disease tolerance
immunometabolism
immunosuppression
itaconate
pulmonary infection
type 6 secretion system
Journal
Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170
Informations de publication
Date de publication:
03 05 2022
03 05 2022
Historique:
received:
29
10
2021
revised:
18
01
2022
accepted:
22
03
2022
pubmed:
13
4
2022
medline:
7
5
2022
entrez:
12
4
2022
Statut:
ppublish
Résumé
K. pneumoniae sequence type 258 (Kp ST258) is a major cause of healthcare-associated pneumonia. However, it remains unclear how it causes protracted courses of infection in spite of its expression of immunostimulatory lipopolysaccharide, which should activate a brisk inflammatory response and bacterial clearance. We predicted that the metabolic stress induced by the bacteria in the host cells shapes an immune response that tolerates infection. We combined in situ metabolic imaging and transcriptional analyses to demonstrate that Kp ST258 activates host glutaminolysis and fatty acid oxidation. This response creates an oxidant-rich microenvironment conducive to the accumulation of anti-inflammatory myeloid cells. In this setting, metabolically active Kp ST258 elicits a disease-tolerant immune response. The bacteria, in turn, adapt to airway oxidants by upregulating the type VI secretion system, which is highly conserved across ST258 strains worldwide. Thus, much of the global success of Kp ST258 in hospital settings can be explained by the metabolic activity provoked in the host that promotes disease tolerance.
Identifiants
pubmed: 35413274
pii: S1550-4131(22)00097-3
doi: 10.1016/j.cmet.2022.03.009
pmc: PMC9081115
mid: NIHMS1793943
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
761-774.e9Subventions
Organisme : NIAID NIH HHS
ID : T32 AI100852
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR027050
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA209896
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL138289
Pays : United States
Organisme : NIAID NIH HHS
ID : K08 AI146284
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL135800
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA140271
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI116939
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA087497
Pays : United States
Organisme : NCI NIH HHS
ID : F30 CA265288
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA111289
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001873
Pays : United States
Organisme : NINDS NIH HHS
ID : R33 NS109407
Pays : United States
Organisme : NHLBI NIH HHS
ID : K99 HL157550
Pays : United States
Organisme : NINDS NIH HHS
ID : R61 NS109407
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA013696
Pays : United States
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests B.R.S. is an inventor on patents and patent applications related to GPX4 and ferroptosis, a consultant to and co-founder of Inzen Therapeutics and Nevrox Limited, and a member of the Scientific Advisory Board of Weatherwax Biotechnologies Corporation. The other authors declare no competing interests.
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