TY - JOUR
T1 - Yersinia pseudotuberculosis supports Th17 differentiation and limits de novo regulatory T cell induction by directly interfering with T cell receptor signaling
AU - Pasztoi, Maria
AU - Bonifacius, Agnes
AU - Pezoldt, Joern
AU - Kulkarni, Devesha
AU - Niemz, Jana
AU - Yang, Juhao
AU - Teich, René
AU - Hajek, Janina
AU - Pisano, Fabio
AU - Rohde, Manfred
AU - Dersch, Petra
AU - Huehn, Jochen
N1 - Funding Information:
We thank Lothar Groebe for cell sorting, Fabio Pisano for support during infection experiments, Maria Ebel, Tanja Krause, and Karin Paduch for technical assistance. This work was supported by the Deutsche Forschungsgemeinschaft (SFB854 project B16 and SPP1656).
Publisher Copyright:
© 2017, The Author(s).
PY - 2017/8/1
Y1 - 2017/8/1
N2 - 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.
AB - 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.
KW - Intestinal infections
KW - Regulatory T cells
KW - TCR signaling
KW - Th17 cells
KW - Yersinia pseudotuberculosis
UR - http://www.scopus.com/inward/record.url?scp=85017156064&partnerID=8YFLogxK
U2 - 10.1007/s00018-017-2516-y
DO - 10.1007/s00018-017-2516-y
M3 - Article
C2 - 28378044
AN - SCOPUS:85017156064
VL - 74
SP - 2839
EP - 2850
JO - Cellular and Molecular Life Sciences
JF - Cellular and Molecular Life Sciences
SN - 1420-682X
IS - 15
ER -