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A metabolism-based quorum sensing mechanism contributes to termination of inflammatory responses

Abstract : Recruitment of immune cells during infection is essential to fueling the immune response but can also trigger immunopathology. A critical question is how the immune system can sense inflammation levels and self-adjust accordingly to limit tissue damage while removing the pathogen. During my Ph.D. I studied the self-resolving cutaneous infection with Leishmania major parasites where tissue damage arises when inflammation is allowed to become excessive. At the site of infection, the immune reaction is driven by recruited monocyte-derived cells that represents the major population of infected cells and are also actively involved in fighting the infection. They secrete pro-inflammatory cytokines but also produce nitric oxide (NO), critical to regulate the outcome of the infection: iNOS KO mice are susceptible and do not control the parasite load, subsequently developing severe tissue damage because of excessive immune cell infiltration. My work demonstrated that monocyte-derived cells at the site of infection are regulated by NO that limits their cellular respiration, lowers their energetic resources and consequently their activity in vivo. This regulation relies on tissue-wide NO diffusion and only exists when a sufficient cell density has been reached, revealing that monocyte-derived cells are endowed with a quorum sensing mechanism that adjusts their population size and activity in time and space to avoid immunopathology.
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Jérémy Postat. A metabolism-based quorum sensing mechanism contributes to termination of inflammatory responses. Immunology. Université Sorbonne Paris Cité, 2018. English. ⟨NNT : 2018USPCC309⟩. ⟨tel-02928366⟩

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