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IFN-γ primes bone marrow neutrophils to acquire regulatory functions in severe viral respiratory infections
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Edité par CCSD ; American Association for the Advancement of Science (AAAS) -
International audience. Neutrophil subsets endowed with regulatory/suppressive properties are widely regarded as deleterious immune cells that can jeopardize antitumoral response and/or antimicrobial resistance. Here, we describe a sizeable fraction of neutrophils characterized by the expression of programmed death-ligand 1 (PD-L1) in biological fluids of humans and mice with severe viral respiratory infections (VRI). Biological and transcriptomic approaches indicated that VRI-driven PD-L1 + neutrophils are endowed with potent regulatory functions and reduced classical antimicrobial properties, as compared to their PD-L1 -counterpart. VRI-induced regulatory PD-L1 + neutrophils were generated remotely in the bone marrow in an IFN-γ-dependent manner and were quickly mobilized into the inflamed lungs where they fulfilled their maturation. Neutrophil depletion and PD-L1 blockade during experimental VRI resulted in higher mortality, increased local inflammation, and reduced expression of resolving factors. These findings suggest that PD-L1 + neutrophils are important players in disease tolerance by mitigating local inflammation during severe VRI and that they may constitute relevant targets for future immune interventions.
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