Impact of CCR7 on T-Cell Response and Susceptibility to Yersinia pseudotuberculosis Infection

J Infect Dis. 2017 Sep 15;216(6):752-760. doi: 10.1093/infdis/jix037.

Abstract

Background: To successfully limit pathogen dissemination, an immunological link between the entry tissue of the pathogen and the underlying secondary lymphoid organs (SLOs) needs to be established to prime adaptive immune responses. Here, the prerequisite of CCR7 to mount host immune responses within SLOs during gastrointestinal Yersinia pseudotuberculosis infection to limit pathogen spread was investigated.

Methods: Survival, bacterial dissemination, and intestinal and systemic pathology of wild-type and CCR7-/- mice were assessed and correlated to the presence of immune cell subsets and cytokine responses throughout the course of infection.

Results: The CCR7-/- mice show a significantly higher morbidity and are more prone to pathogen dissemination and intestinal and systemic inflammation during the oral route of infection. Significant impact of CCR7 deficiency over the course of infection on several immunological parameters were observed (ie, elevated neutrophil-dominated innate immune response in Peyer's patches, limited dendritic cell migration to mesenteric lymph nodes [mLNs] causing reduced T cell-mediated adaptive immune responses (in particular Th17-like responses) in mLNs).

Conclusions: Our work indicates that CCR7 is required to mount a robust immune response against enteropathogenic Y. pseudotuberculosis by promoting Th17-like responses in mLNs.

Keywords: CCR7; Peyer’s Patches; T cells; Yersinia pseudotuberculosis; dendritic cells; mesenteric lymph nodes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement
  • Dendritic Cells / immunology
  • Genetic Predisposition to Disease*
  • Host-Pathogen Interactions / genetics
  • Intestines / immunology
  • Intestines / microbiology
  • Lymph Nodes / immunology
  • Lymph Nodes / microbiology
  • Mice
  • Myeloid Cells / immunology
  • Peyer's Patches / immunology
  • Peyer's Patches / microbiology
  • Receptors, CCR7 / genetics
  • Receptors, CCR7 / immunology*
  • Th17 Cells / immunology*
  • Yersinia pseudotuberculosis
  • Yersinia pseudotuberculosis Infections / genetics
  • Yersinia pseudotuberculosis Infections / immunology*

Substances

  • Ccr7 protein, mouse
  • Receptors, CCR7