title: Yersinia pseudotuberculosis supports Th17 differentiation and limits de novo regulatory T cell induction by directly interfering with T cell receptor signaling.
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.
authors.affiliation: Department Experimental Immunology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124, Brunswick, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Pasztoi
authors.affiliation: Department Experimental Immunology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124, Brunswick, Germany.
authors.forename: Agnes
authors.initials: A
authors.lastname: Bonifacius
authors.affiliation: Department Experimental Immunology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124, Brunswick, Germany.
authors.forename: Joern
authors.initials: J
authors.lastname: Pezoldt
authors.affiliation: Department Experimental Immunology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124, Brunswick, Germany.
authors.forename: Devesha
authors.initials: D
authors.lastname: Kulkarni
authors.affiliation: Department Experimental Immunology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124, Brunswick, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Niemz
authors.affiliation: Department Experimental Immunology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124, Brunswick, Germany.
authors.forename: Juhao
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department Experimental Immunology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124, Brunswick, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Teich
authors.affiliation: Department Molecular Infection Biology, Helmholtz Centre for Infection Research, 38124, Brunswick, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Hajek
authors.affiliation: Department Molecular Infection Biology, Helmholtz Centre for Infection Research, 38124, Brunswick, Germany.
authors.forename: Fabio
authors.initials: F
authors.lastname: Pisano
authors.affiliation: Central Facility for Microscopy, Helmholtz Centre for Infection Research, 38124, Brunswick, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Rohde
authors.affiliation: Department Molecular Infection Biology, Helmholtz Centre for Infection Research, 38124, Brunswick, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Dersch
authors.affiliation: Department Experimental Immunology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124, Brunswick, Germany. jochen.huehn@helmholtz-hzi.de.
authors.forename: Jochen
authors.initials: J
authors.lastname: Huehn
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D002454:Cell Differentiation; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D054884:Host-Pathogen Interactions; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D008807:Mice, Inbred BALB C; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000382:microbiology*; D058504:Th17 Cells / Q000276:immunology / Q000382:microbiology*; D015011:Yersinia pseudotuberculosis / Q000276:immunology* / Q000502:physiology; D015012:Yersinia pseudotuberculosis Infections / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D011948:Receptors, Antigen, T-Cell
keywords: Intestinal infections; Regulatory T cells; TCR signaling; Th17 cells; Yersinia pseudotuberculosis