Inulin Prebiotic Protects against Lethal Pseudomonas aeruginosa Acute Infection via ?d T Cell Activation

Pseudomonas aeruginosa (P. aeruginosa) causes harmful lung infections, especially in immunocompromised patients. The immune system and Interleukin (IL)-17-producing ?d T cells (?d T) are critical in controlling these infections in mice. The gut microbiota modulates host immunity in both cancer and infection contexts. Nutritional intervention is a powerful means of modulating both microbiota composition and functions, and subsequently the host's immune status. We have recently shown that inulin prebiotic supplementation triggers systemic ?d T activation in a cancer context. We hypothesized that prophylactic supplementation with inulin might protect mice from lethal P. aeruginosa acute lung infection in a ?d T-dependent manner. C57Bl/6 mice were supplemented with inulin for 15 days before the lethal P. aeruginosa lung infection, administered intranasally. We demonstrate that prophylactic inulin supplementation triggers a higher proportion of ?d T in the blood, accompanied by a higher infiltration of IL-17-producing ?d T within the lungs, and protects 33% of infected mice from death. This observation relies on ?d T, as in vivo ?d TcR blocking using a monoclonal antibody completely abrogates inulin-mediated protection. Overall, our data indicate that inulin supplementation triggers systemic ?d T activation, and could help resolve lung P. aeruginosa infections. Moreover, our data suggest that nutritional intervention might be a powerful way to prevent/reduce infection-related mortality, by reinforcing the microbiota-dependent immune system.