Journal of neuroinflammation
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.
Adaptive Immunity, Animals, Bacterial Load, Brain Abscess, Cell Movement, Immunity, Innate, Mice, Mice, Inbred C57BL, Mice, Knockout, Natural Killer T-Cells, Receptors, Antigen, T-Cell, gamma-delta, Receptors, Interleukin-17, Signal Transduction, Staphylococcal Infections, T-Lymphocyte Subsets
This work is licensed under a Creative Commons Attribution 2.0 License. Creative Commons Attribution License 2.0
Vidlak, Debbie and Kielian, Tammy, "Differential effects of interleukin-17 receptor signaling on innate and adaptive immunity during central nervous system bacterial infection." (2012). Journal Articles: Pathology and Microbiology. 40.