RT Journal Article
SR Electronic
T1 Dual neutrophil subsets exacerbate or suppress inflammation in tuberculosis via IL-1β or PD-L1
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202402623
DO 10.26508/lsa.202402623
VO 7
IS 7
A1 Doz-Deblauwe, Emilie
A1 Bounab, Badreddine
A1 Carreras, Florence
A1 Fahel, Julia S
A1 Oliveira, Sergio C
A1 Lamkanfi, Mohamed
A1 Le Vern, Yves
A1 Germon, Pierre
A1 Pichon, Julien
A1 Kempf, Florent
A1 Paget, Christophe
A1 Remot, Aude
A1 Winter, Nathalie
YR 2024
UL https://www.life-science-alliance.org/content/7/7/e202402623.abstract
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.