Yersinia pseudotuberculosis supports Th17 differentiation and limits de novo regulatory T cell induction by directly interfering with T cell receptor signaling

Maria Pasztoi, Agnes Bonifacius, Joern Pezoldt, Devesha Kulkarni, Jana Niemz, Juhao Yang, René Teich, Janina Hajek, Fabio Pisano, Manfred Rohde, Petra Dersch, Jochen Huehn

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Adaptive immunity critically contributes to control acute infection with enteropathogenic Yersinia pseudotuberculosis; however, the role of CD4+ T cell subsets in establishing infection and allowing pathogen persistence remains elusive. Here, we assessed the modulatory capacity of Y. pseudotuberculosis on CD4+ T cell differentiation. Using in vivo assays, we report that infection with Y. pseudotuberculosis resulted in enhanced priming of IL-17-producing T cells (Th17 cells), whereas induction of Foxp3+ regulatory T cells (Tregs) was severely disrupted in gut-draining mesenteric lymph nodes (mLNs), in line with altered frequencies of tolerogenic and proinflammatory dendritic cell (DC) subsets within mLNs. Additionally, by using a DC-free in vitro system, we could demonstrate that Y. pseudotuberculosis can directly modulate T cell receptor (TCR) downstream signaling within naïve CD4+ T cells and Tregs via injection of effector molecules through the type III secretion system, thereby affecting their functional properties. Importantly, modulation of naïve CD4+ T cells by Y. pseudotuberculosis resulted in an enhanced Th17 differentiation and decreased induction of Foxp3+ Tregs in vitro. These findings shed light to the adjustment of the Th17-Treg axis in response to acute Y. pseudotuberculosis infection and highlight the direct modulation of CD4+ T cell subsets by altering their TCR downstream signaling.

Original languageEnglish
Pages (from-to)2839-2850
Number of pages12
JournalCellular and Molecular Life Sciences
Volume74
Issue number15
DOIs
StatePublished - Aug 1 2017
Externally publishedYes

Keywords

  • Intestinal infections
  • Regulatory T cells
  • TCR signaling
  • Th17 cells
  • Yersinia pseudotuberculosis

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