Interleukin-17 Is a Critical Mediator of Vaccine-Induced Reduction of Helicobacter Infection in the Mouse Model

Velin, Dominique; Favre, Laurent; Bernasconi, Eric; Bachmann, Daniel; Pythoud, Catherine; Saïji, Essia; Bouzourène, Hanifa; Michetti, Pierre

doi:10.1053/j.gastro.2009.02.077

Cited by 116 publications

(151 citation statements)

References 29 publications

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“…Indeed, a recent report observed that CT is able to generate Th17 cells in an IL-6-dependent manner (11), and vaccines containing CT or Escherichia coli heat-labile toxin also induced IL-17 (36)(37)(38)(39), but the mechanisms involved and the role of IL-17 in mediating adjuvant effects (i.e., antibody responses and protection against infection) were not explored. In addition, our data show that a natural biological molecule such as CT induces DCs to secrete a complex mixture of products that are required to act in combination to determine T-cell fate (Fig.…”

Section: Discussionmentioning

confidence: 99%

Mucosal adjuvant activity of cholera toxin requires Th17 cells and protects against inhalation anthrax

Datta

Sabet²,

Nguyen³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

145

129

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Cholera toxin (CT) elicits a mucosal immune response in mice when used as a vaccine adjuvant. The mechanisms by which CT exerts its adjuvant effects are incompletely understood. We show that protection against inhalation anthrax by an irradiated spore vaccine depends on CT-mediated induction of IL-17-producing CD4 Th17 cells. Furthermore, IL-17 is involved in the induction of serum and mucosal antibody responses by CT. Th17 cells induced by CT have a unique cytokine profile compared with those induced by IL-6 and TGF-β, and their induction by CT requires cAMP-dependent secretion of IL-1β and β-calcitonin gene-related peptide by dendritic cells. These findings demonstrate that Th17 cells mediate mucosal adjuvant effects of CT and identify previously unexplored pathways involved in Th17 induction that could be targeted for development of unique mucosal adjuvants.IL-17 | dendritic cell | T cell | vaccine | cAMP

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Section: Discussionmentioning

confidence: 99%

Mucosal adjuvant activity of cholera toxin requires Th17 cells and protects against inhalation anthrax

Datta

Sabet²,

Nguyen³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

145

129

View full text Add to dashboard Cite

show abstract

“…En un estudio se consiguió una disminución en la carga bacteriana utilizando IL-17 y se demostró que el bloqueo de la función de IL-17 disminuía significativamente la eficacia de la inmunización contra H. pylori 86 . Otros investigadores encontraron inmunidad esterilizante en ratones infectados a través del uso de terapia con IL-12, para promover una respuesta Th1, aún en ausencia de inmunización 39 .…”

Section: Mecanismo De La Inmunidadunclassified

Avances en la búsqueda de la vacuna contra Helicobacter pylori

Urrego

Otero

Trespalacios

2017

revmed

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“…In the gastrointestinal tract, induction of mucosal IL-17 secretion Correspondence: Dr. Stephen E. Girardin e-mail: stephen.girardin@utoronto.ca was shown to be associated with protection against Salmonella enterica serovar Typhymurium [1], Citrobacter rodentium [2], and Helicobacter species [3]. IL-17 exerts its mucosal protection at least in part through an increase of neutrophil recruitment and neutrophil-driven defense mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Constitutive induction of intestinal Tc17 cells in the absence of hematopoietic cell‐specific MHC class II expression

et al. 2013

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The enteric pathogen Citrobacter rodentium induces a mucosal IL-17 response in CD4 + T helper (Th17) cells that is dependent on the Nod-like receptors Nod1 and Nod2. Here, we sought to determine whether this early Th17 response required antigen presentation by major histocompatibility complex class II (MHCII) for full induction. At early phases of C. rodentium infection, we observed that the intestinal mucosal Th17 response was fully blunted in irradiated mice reconstituted with MHCII-deficient (MHCII −/− →WT) hematopoietic cells. Surprisingly, we also observed a substantial increase in the relative frequency of IL-17 + CD8 + CD4 − TCR-β + cells (Tc17 cells) and FOXP3 + CD8 + CD4 − TCR-β + cells in the lamina propria and intraepithelial lymphocyte compartment of MHCII −/− →WT mice compared with that in WT→WT counterparts. Moreover, MHCII −/− →WT mice displayed increased susceptibility, increased bacterial translocation to deeper organs, and more severe colonic histopathology after infection with C. rodentium. Finally, a similar phenotype was observed in mice deficient for CIITA, a transcriptional regulator of MHCII expression. Together, these results indicate that MHCII is required to mount early mucosal Th17 responses to an enteric pathogen, and that MHCII regulates the induction of atypical CD8 + T-cell subsets, such as Tc17 cells and FOXP3 + CD8 + cells, in vivo. Keywords:Citrobacter rodentium r FOXP3 + CD8 + r IL-17 r MHC class II r Tc17Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionInterleukin (IL)-17A (herein referred to as IL-17) is a cytokine critical for host defense against pathogens at mucosal surfaces. In the gastrointestinal tract, induction of mucosal IL-17 secretion Correspondence: Dr. Stephen E. Girardin e-mail: stephen.girardin@utoronto.ca was shown to be associated with protection against Salmonella enterica serovar Typhymurium [1], Citrobacter rodentium [2], and Helicobacter species [3]. IL-17 exerts its mucosal protection at least in part through an increase of neutrophil recruitment and neutrophil-driven defense mechanisms. In addition, IL-17 acts in concert with IL-22 to enhance epithelial innate functions, such as antimicrobial peptide secretion, mucus secretion, proliferation, and renewal [4,5].IL-17 can be secreted by a number of cell populations, including CD4 + T helper (Th17) cells, γδ T cells, innate lymphoid cells (that C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2013. 43: 2896-2906 Immunity to infection 2897 include lymphoid tissue inducer cells) and natural killer T (NKT) cells [6][7][8][9][10][11]. In humans, Th17 cells appear to represent the major cell population that produces IL-17 in the intestine under normal conditions, whereas in mice IL-17 is mainly produced by Th17 and γδ T cells. Th17 cell differentiation is mediated by the cytokines IL-6 and TGF-β, whereas IL-23 and IL-1β contribute to the full activation of these cells [6,12,13]. In addition to the c...

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Interleukin-17 Is a Critical Mediator of Vaccine-Induced Reduction of Helicobacter Infection in the Mouse Model

Cited by 116 publications

References 29 publications

Mucosal adjuvant activity of cholera toxin requires Th17 cells and protects against inhalation anthrax

Mucosal adjuvant activity of cholera toxin requires Th17 cells and protects against inhalation anthrax

Avances en la búsqueda de la vacuna contra Helicobacter pylori

Constitutive induction of intestinal Tc17 cells in the absence of hematopoietic cell‐specific MHC class II expression

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