PT  - JOURNAL ARTICLE
AU  - Doz-Deblauwe, Emilie
AU  - Bounab, Badreddine
AU  - Carreras, Florence
AU  - Fahel, Julia S
AU  - Oliveira, Sergio C
AU  - Lamkanfi, Mohamed
AU  - Le Vern, Yves
AU  - Germon, Pierre
AU  - Pichon, Julien
AU  - Kempf, Florent
AU  - Paget, Christophe
AU  - Remot, Aude
AU  - Winter, Nathalie
TI  - Dual neutrophil subsets exacerbate or suppress inflammation in tuberculosis via IL-1β or PD-L1
AID  - 10.26508/lsa.202402623
DP  - 2024 Jul 01
TA  - Life Science Alliance
PG  - e202402623
VI  - 7
IP  - 7
4099  - https://www.life-science-alliance.org/content/7/7/e202402623.short
4100  - https://www.life-science-alliance.org/content/7/7/e202402623.full
SO  - Life Sci. Alliance2024 Jul 01; 7
AB  - Neutrophils can be beneficial or deleterious during tuberculosis (TB). Based on the expression of MHC-II and programmed death ligand 1 (PD-L1), we distinguished two functionally and transcriptionally distinct neutrophil subsets in the lungs of mice infected with mycobacteria. Inflammatory [MHC-II−, PD-L1lo] neutrophils produced inflammasome-dependent IL-1β in the lungs in response to virulent mycobacteria and “accelerated” deleterious inflammation, which was highly exacerbated in IFN-γR−/− mice. Regulatory [MHC-II+, PD-L1hi] neutrophils “brake” inflammation by suppressing T-cell proliferation and IFN-γ production. Such beneficial regulation, which depends on PD-L1, is controlled by IFN-γR signaling in neutrophils. The hypervirulent HN878 strain from the Beijing genotype curbed PD-L1 expression by regulatory neutrophils, abolishing the braking function and driving deleterious hyperinflammation in the lungs. These findings add a layer of complexity to the roles played by neutrophils in TB and may explain the reactivation of this disease observed in cancer patients treated with anti-PD-L1.All data are available in the main text or supplementary materials. Transcriptomic data are available using the BioProject accession number PRJNA1026083.