IL-17 receptor signaling is required to control polymicrobial sepsis.
Sepsis is a systemic inflammatory response resulting from the inability of the host to contain the infection locally. Previously, we 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-17R signaling in polymicrobial sepsis induced by cecal ligation and puncture (CLP). It was observed that IL-17R-deficient mice, subjected to CLP-induced non-severe sepsis, show reduced neutrophil recruitment into the peritoneal cavity, spread of infection, and increased systemic inflammatory response as compared with C57BL/6 littermates. As a consequence, the mice showed an increased mortality rate. The ability of IL-17 to induce neutrophil migration was demonstrated in vivo and in vitro. Beside its role in neutrophil recruitment to the infection focus, IL-17 enhanced the microbicidal activity of the migrating neutrophils by a mechanism dependent on NO. Therefore, IL-17 plays a critical role in host protection during polymicrobial sepsis.
Freitas
Andressa
A
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
Alves-Filho
José C
JC
Victoni
Tatiana
T
Secher
Thomas
T
Lemos
Henrique P
HP
Sônego
Fabiane
F
Cunha
Fernando Q
FQ
Ryffel
Bernhard
B
D000818:Animals; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005334:Fever / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D053722:Receptors, Interleukin-17 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D018805:Sepsis / Q000276:immunology* / Q000382:microbiology*; D015398:Signal Transduction / Q000276:immunology*
D016207:Cytokines; D053722:Receptors, Interleukin-17