Differential effects of interleukin-17 receptor signaling on innate and adaptive immunity during central nervous system bacterial infection

Although il-17a (commonly referred to as il-17) has been implicated in the pathogenesis of central nervous system (cns) autoimmune disease,its role during cns bacterial infections remains unclear. to evaluate the broader impact of il-17 family members in the context of cns infection,we utilized il-17 receptor (il-17r) knockout (ko) mice that lack the ability to respond to il-17,il-17f and il-17e (il-25). in this article,we demonstrate that il-17r signaling regulates bacterial clearance as well as natural killer t (nkt) cell and gamma-delta (γδ) t cell infiltrates during staphylococcus aureus-induced brain abscess formation. specifically,when compared with wild-type (wt) animals,il-17r ko mice exhibited elevated bacterial burdens at days 7 and 14 following s. aureus infection. additionally,il-17r ko animals displayed elevated neutrophil chemokine production,revealing the ability to compensate for the lack of il-17r activity. despite these differences,innate immune cell recruitment into brain abscesses was similar in il-17r ko and wt mice,whereas il-17r signaling exerted a greater influence on adaptive immune cell recruitment. in particular,γδ t cell influx was increased in il-17r ko mice at day 7 post-infection. in addition,nk1.1high infiltrates were absent in brain abscesses of il-17r ko animals and,surprisingly,were rarely detected in the livers of uninfected il-17r ko mice. although il-17 is a key regulator of neutrophils in other infection models,our data implicate an important role for il-17r signaling in regulating adaptive immunity during cns bacterial infection. © 2012 vidlak and kielian; licensee biomed central ltd.