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Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2022

Beneficial effects of citrulline enteral administration on sepsis-induced T cell mitochondrial dysfunction

Résumé

Severe sepsis induces a sustained immune dysfunction associated with poor clinical behavior. In particular, lymphopenia along with increased lymphocyte apoptosis and decreased lymphocyte proliferation, enhanced circulating regulatory T cells (Treg), and the emergence of myeloid-derived suppressor cells (MDSCs) have all been associated with persistent organ dysfunction, secondary infections, and late mortality. The mechanisms involved in MDSC-mediated T cell dysfunction during sepsis share some features with those described in malignancies such as arginine deprivation. We hypothesized that increasing arginine availability would restore T cell function and decrease sepsis-induced immunosuppression. Using a mouse model of sepsis based on cecal ligation and puncture and secondary pneumonia triggered by methicillin-resistant Staphylococcus aureus inoculation, we demonstrated that citrulline administration was more efficient than arginine in increasing arginine plasma levels and restoring T cell mitochondrial function and proliferation while reducing sepsis-induced Treg and MDSC expansion. Because there is no specific therapeutic strategy to restore immune function after sepsis, we believe that our study provides evidence for developing citrulline-based clinical studies in sepsis.
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Dates et versions

hal-03594344 , version 1 (31-05-2022)

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Paternité - Pas d'utilisation commerciale - Pas de modification

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Florian Reizine, Murielle Grégoire, Mathieu Lesouhaitier, Valentin Coirier, Juliette Gauthier, et al.. Beneficial effects of citrulline enteral administration on sepsis-induced T cell mitochondrial dysfunction. Proceedings of the National Academy of Sciences of the United States of America, 2022, 119 (8), pp.e2115139119. ⟨10.1073/pnas.2115139119⟩. ⟨hal-03594344⟩
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