Lower female survival from an opportunistic infection reveals progesterone-driven sex bias in trained immunity.
Burkholderia gladioli
CP: Immunology
glycolytic capacity
innate immune memory
oppotunistic infection
progesterone
progesterone receptor
sex as a biological variable
sex bias
trained immunity
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
29 08 2023
29 08 2023
Historique:
received:
19
01
2023
revised:
08
06
2023
accepted:
03
08
2023
medline:
4
9
2023
pubmed:
17
8
2023
entrez:
17
8
2023
Statut:
ppublish
Résumé
Immune responses differ between females and males, although such sex-based variance is incompletely understood. Observing that bacteremia of the opportunistic pathogen Burkholderia gladioli caused many more deaths of female than male mice bearing genetic deficiencies in adaptive immunity, we determined that this was associated with sex bias in the innate immune memory response called trained immunity. Female attenuation of trained immunity varies with estrous cycle stage and correlates with serum progesterone, a hormone that decreases glycolytic capacity and recall cytokine secretion induced by antigen non-specific stimuli. Progesterone receptor antagonism rescues female trained immune responses and survival from controlled B. gladioli infection to magnitudes similar to those of males. These data demonstrate progesterone-dependent sex bias in trained immunity where attenuation of female responses is associated with survival outcomes from opportunistic infection.
Identifiants
pubmed: 37590139
pii: S2211-1247(23)01018-5
doi: 10.1016/j.celrep.2023.113007
pmc: PMC10528383
mid: NIHMS1928299
pii:
doi:
Substances chimiques
Progesterone
4G7DS2Q64Y
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
113007Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM103841
Pays : United States
Organisme : NCI NIH HHS
ID : R33 CA228979
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008396
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA244314
Pays : United States
Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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