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

J Neuroinflammation. 2012 Jun 15:9:128. doi: 10.1186/1742-2094-9-128.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptive Immunity* / genetics
  • Animals
  • Bacterial Load / genetics
  • Brain Abscess / genetics
  • Brain Abscess / immunology*
  • Brain Abscess / microbiology*
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Immunity, Innate* / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Natural Killer T-Cells / immunology
  • Natural Killer T-Cells / metabolism
  • Natural Killer T-Cells / pathology
  • Receptors, Antigen, T-Cell, gamma-delta / deficiency
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / physiology*
  • Receptors, Interleukin-17 / deficiency
  • Receptors, Interleukin-17 / genetics
  • Receptors, Interleukin-17 / physiology*
  • Signal Transduction* / genetics
  • Staphylococcal Infections / genetics
  • Staphylococcal Infections / immunology*
  • Staphylococcal Infections / metabolism
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism

Substances

  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Interleukin-17