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IL-17 receptor signaling is required to control polymicrobial sepsis
Critical Care volume 13, Article number: P8 (2009)
Sepsis is a systemic inflammatory response resulting from the inability of the host to contain the infection locally. We previously demonstrated that during severe sepsis there is a marked failure of neutrophil migration to the infection site, which contributes to dissemination of infection, resulting in high mortality. IL-17 plays an important role in neutrophil recruitment. Herein, we investigated the role of IL-17 receptor signaling in polymicrobial sepsis induced by cecal ligation and puncture (CLP).
Methods and results
Adult C57BL/6 WT and IL-17 receptor KO mice were subjected to nonsevere (NS-CLP) sepsis. Intraperitoneal neutrophil migration, bacteremia, cytokines and liver injury were evaluated 6 hours after surgery. The ability of IL-17 to mediate the neutrophil microbicidal activity in vitro, as well the neutrophil migration in vivo and in vitro, were also evaluated. It was observed that IL-17R-deficient mice, subjected to CLP-induced nonsevere sepsis, show reduced neutrophil recruitment into the peritoneal cavity, spread of infection, and increased systemic inflammatory response as compared with BL6 littermates. As a consequence, the mice showed an increased mortality rate. Moreover, IL-17 induced intraperitoneal neutrophil migration in vivo and in vitro. Besides, we demonstrated that neutrophils harvested from IL-17R-defective mice already show reduced microbicidal activity, compared with WT neutrophils, suggesting a physiological role of IL-17R signaling in the microbicidal activity of neutrophils. Furthermore, WT neutrophils treated with IL-17 showed strong enhancement of microbicidal activity by a mechanism dependent on nitric oxide.
Taken together, our results demonstrate that IL-17 receptor signalization plays a critical role in host protection during polymicrobial sepsis.
Supported by FAPESP/CNPq/FAEPA.
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Freitas, A. IL-17 receptor signaling is required to control polymicrobial sepsis. Crit Care 13 (Suppl 3), P8 (2009). https://doi.org/10.1186/cc7810