Doz-Deblauwe, E.; Bounab, B.; Carreras, F.; Silverira-Fahel, J.; Oliveira, S. C.; Lamkanfi, M.; Le Vern, Y.; GERMON, P.; Pichon, J.; Kempf, F.; Paget, C.; Remot, A.; Winter, N.

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-L1 low] neutrophils produced inflammasome-dependent IL-1{beta} in the lungs in response to virulent mycobacteria and \'\'accelerated\'\' deleterious inflammation, which was highly exacerbated in IFN-{gamma}R-/- mice. Regulatory [MHC-II+, PD-L1 high] neutrophils \'\'brake\'\' inflammation by suppressing T-cell proliferation and IFN-{gamma} production. Such beneficial regulation, which depends on PD-L1, is controlled by IFN-{gamma}R 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 hyper-inflammation 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.