Dual neutrophil subsets accelerate or brake inflammation in tuberculosis
Résumé
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 lo ] neutrophils produced inflammasome-dependent IL-1b in the lungs in response to virulent mycobacteria and "accelerated" deleterious inflammation, which was highly exacerbated in IFN-gR -/-mice. Regulatory [MHC-II+, PD-L1 hi ] neutrophils "brake" inflammation by suppressing T-cell proliferation and IFN-g production. Such beneficial regulation, which depends on PD-L1, is controlled by IFN-gR signaling in neutrophils. 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.
Domaines
Immunologie| Origine | Fichiers produits par l'(les) auteur(s) |
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