Induction of TGF-β1 and TGF-β1-dependent predominant Th17 differentiation by group A streptococcal infection

Beinan Wang, Thamotharampillai Dileepan, Sarah Briscoe, Kendra A. Hyland, Johnthomas Kang, Alexander Khoruts, P. Patrick Cleary

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Recurrent group A Streptococcus (GAS) tonsillitis and associated autoimmune diseases indicate that the immune response to this organism can be ineffective and pathological. TGF-β1 is recognized as an essential signal for generation of regulatory T cells (Tregs) and T helper (Th) 17 cells. Here, the impact of TGF-β1 induction on the Tcell response in mouse nasal-associated lymphoid tissue (NALT) following intranasal (i.n.) infections is investigated. ELISA and TGF-β1-luciferase reporter assays indicated that persistent infection of mouse NALT with GAS sets the stage for TGF-β1 and IL-6 production, signals required for promotion of a Th17 immune response. As predicted, IL-17, the Th17 signature cytokine, was induced in a TGF-β1 signaling-dependent manner in single-cell suspensions of both human tonsils and NALT. Intracellular cytokine staining and flow cytometry demonstrated that CD4+ IL-17+ T cells are the dominant T cells induced in NALT by i.n. infections. Moreover, naive mice acquired the potential to clear GAS by adoptive transfer of CD4+ T cells from immunized IL-17A +/+ mice but not cells from IL-17A-/ - mice. These experiments link specific induction of TGF-β1 by a bacterial infection to an in vivo Th17 immune response and show that this cellular response is sufficient for protection against GAS. The association of a Th17 response with GAS infection reveals a potential mechanism for destructive autoimmune responses in humans.

Original languageEnglish (US)
Pages (from-to)5937-5942
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number13
DOIs
StatePublished - Mar 30 2010

Keywords

  • IL-17
  • Nasal-associated lymphoid tissue
  • Streptococcus pyogenes

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