Monocytes are the main source of STING-mediated IFN-α production - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue EBioMedicine Année : 2022

Monocytes are the main source of STING-mediated IFN-α production

Résumé

Background: Type I interferon (IFN-I) production by plasmacytoid dendritic cells (pDCs) occurs during viral infection, in response to Toll-like receptor 7 (TLR7) stimulation and is more vigorous in females than in males. Whether this sex bias persists in ageing people is currently unknown. In this study, we investigated the effect of sex and aging on IFN-α production induced by PRR agonist ligands. Methods: In a large cohort of individuals from 19 to 97 years old, we measured the production of IFN-α and inflammatory cytokines in whole-blood upon stimulation with either R-848, ODN M362 CpG-C, or cGAMP, which activate the TLR7/8, TLR9 or STING pathways, respectively. We further characterized the cellular sources of IFN-α. Findings: We observed a female predominance in IFN-α production by pDCs in response to TLR7 or TLR9 ligands. The higher TLR7-driven IFN-α production in females was robustly maintained across ages, including the elderly. The sex-bias in TLR9-driven interferon production was lost after age 60, which correlated with the decline in circulating pDCs. By contrast, STING-driven IFN-α production was similar in both sexes, preserved with aging, and correlated with circulating monocyte numbers. Indeed, monocytes were the primary cellular source of IFN-α in response to cGAMP. Interpretation: We show that the sex bias in the TLR7-induced IFN-I production is strongly maintained through ages, and identify monocytes as the main source of IFN-I production via STING pathway.
Fichier principal
Vignette du fichier
1-s2.0-S2352396422002286-main.pdf (2.78 Mo) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03852600 , version 1 (23-11-2022)

Identifiants

Citer

Nicolas Congy-Jolivet, Claire Cenac, Jérôme Dellacasagrande, Bénédicte Puissant-Lubrano, Pol André Apoil, et al.. Monocytes are the main source of STING-mediated IFN-α production. EBioMedicine, 2022, 80, pp.104047. ⟨10.1016/j.ebiom.2022.104047⟩. ⟨hal-03852600⟩
37 Consultations
18 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More