Roles of Toll-like receptor 2 (TLR2) and superantigens on adaptive immune responses during CNS staphylococcal infection

Debbie Vidlak, Monica M. Mariani, Amy Aldrich, Shuliang Liu, Tammy Kielian

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Staphylococcus aureus is a common etiologic agent of brain abscesses and possesses numerous virulence factors that manipulate host immunity. One example is superantigens (SAG) that clonally expand T cell subsets bearing specific Vβ receptors. Toll-like receptor 2 (TLR2) is one receptor implicated in S. aureus recognition. However, the interplay between TLR2, SAG, and adaptive immunity during brain abscess formation has not yet been investigated and could reveal novel insights into host-pathogen interactions for regulating protective immunity. A comprehensive analysis of abscess-associated T cell populations in TLR2 KO and WT mice was performed following infection with a S. aureus clinical isolate. Both natural killer T (NKT) and γδ T cell infiltrates were increased in brain abscesses of TLR2 KO mice and produced more IL-17 and IFN-γ compared to WT populations, which could have resulted from elevated bacterial burdens observed in these animals. Analysis of SAG-reactive T cells revealed a predominant Vβ8.1,8.2 infiltrate reactive with staphylococcal enterotoxin B (SEB), whereas SEA-reactive Vβ11 T cells were less numerous. Brain abscesses of TLR2 KO mice had fewer Vβ8.1,8.2 and Vβ11 T cells and produced less TNF-α and IFN-γ compared to WT animals. Treatment of primary microglia with purified SEB augmented TNF-α production in response to the TLR2 ligand Pam3Cys, which may serve to amplify proinflammatory cascades during CNS S. aureus infection. Collectively, these studies demonstrate that TLR2 impacts adaptive immunity to S. aureus infection and modulates SAG responses.

Original languageEnglish (US)
Pages (from-to)905-914
Number of pages10
JournalBrain, Behavior, and Immunity
Volume25
Issue number5
DOIs
StatePublished - Jul 1 2011

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Keywords

  • Microglia
  • Natural killer T cells
  • Staphylococcal enterotoxin B
  • Staphylococcus aureus
  • Superantigen
  • Toll-like receptor 2
  • γδ T cells

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

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