IFNγ pathway is essential for the immunosuppressive activity of regulatory neutrophils.

International audienceThe role played by neutrophils during Mycobacterium tuberculosis (Mtb) infection, the TB agent, remains unclear. IFNγ is a major cytokine involved in control of Mtb infection and granuloma development. Mice lacking the IFNγ receptor (IFNgR) are extremely susceptible to Mtb infection. PDL1 is a major immune check point, with an important role in the regulation of TB which has been unraveled in Humans treated with anti-PDL1 therapy.Among cells present in granulomas, neutrophils may play beneficial or detrimental roles. They are present in several subtypes. We discovered a population of regulatory neutrophils ((CD11b+/Ly6G+/MHCII+/PDL-1hi), which are phenotypically close to inflammatory neutrophils (CD11b+/Ly6G+/MHCII-/PDL-1lo), but differ in their functional capacity to suppress T lymphocytes (Doz-Deblauwe, Rambault et al., 2021).We analyzed the role of IFNγR signaling on neutrophil recruitment to the lung in response to Mtb. Mtb infected IFNγR-/- mice presented an exacerbation of neutrophil recruitment, essentially inflammatory neutrophils. Their regulatory neutrophils showed a defect in the expression of PDL1 which was associated with a loss of their immunosuppressive capacity. The transfer of competent regulatory neutrophils expressing PDL1 (from WT mice) to IFNgR-/- mice limited lung lesions. This reduction in pulmonary inflammation was associated with reduced recruitment of inflammatory neutrophils.Thus, PDL1 is essential for the immunosuppressive activity of regulatory neutrophils and its expression was dependant of the IFNgR pathway. Moreover, regulatory neutrophils are important in the control of inflammatory neutrophil recruitment. Our results suggest that IFNgR pathway is essential for the immunosuppressive activities of regulatory neutrophils