Regulatory neutrophils are a possible signature of granuloma formation.

Abstract

International audienceTuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), induces granuloma formation in the lung, which encapsulated form is the characteristic and final stage of the pathology. C3HeB/FeJ are the only mice able to form an encapsulated granuloma. This model also reproduces the dichotomy of physiopathology: active (uncontrolled) and latent (controlled) TB.Neutrophils play a key role in all stages of the granuloma's life. They are present in several subtypes. We discovered a population of regulatory neutrophils ((CD11b+/Ly6G+/MHCII+/PDL-1hi), which are phenotypically close to the classic, inflammatory neutrophils (CD11b+/Ly6G+/MHCII-/PDL-1lo), but differ in their functional capacity to suppress T lymphocytes (Doz-Deblauwe, Rambault et al., 2021).The role of inflammatory versus regulatory neutrophils, in the maturation and evolution of the TB granuloma, is yet unknown. We infected C3HeB/FeJ mice with the virulent Mtb HN878. 80% of the animals displayed limited survival, a high bacterial load and an hyperinflammation in the lungs. Lung lesions were extensive and poorly organized. The majority of neutrophils (90%) had an inflammatory phenotype. In contrast, animals that did not succumb to infection (20%) showed no signs of morbidity, had a lower bacterial load and less neutrophil recruitment in the lung. The majority of lesions were encapsulated, and correlated with a controlled bacterial load. Interestingly, regulatory neutrophils recruited represented 50% of total neutrophils and they strongly express PDL-1 (a major immune check point).Our results suggest that these regulatory neutrophils are a signature of efficient granuloma formation with infection control