Increased susceptibility to oral Trichuris muris infection in the specific absence of CXCR5+ CD11c+ cells

Parasite Immunol. 2018 Aug;40(8):e12566. doi: 10.1111/pim.12566.

Abstract

Trichuris muris is a natural mouse helminth pathogen which establishes infection specifically in the caecum and proximal colon. The rapid expulsion of T. muris in resistant mouse strains is associated with the induction of a protective T helper cell type 2 (Th2)-polarized immune response. Susceptible mouse strains, in contrast, mount an inappropriate Th1 response to T. muris infection. Expression of the chemokine CXCL13 by stromal follicular dendritic cells attracts CXCR5-expressing cells towards the B-cell follicles. Previous studies using a complex in vivo depletion model have suggested that CXCR5-expressing conventional dendritic cells (cDC) help regulate the induction of Th2-polarized responses. Here, transgenic mice with CXCR5 deficiency specifically restricted to CD11c+ cells were used to determine whether the specific absence CXCR5 on CD11c+ cells such as cDC would influence susceptibility to oral T. muris infection by affecting the Th1/Th2 balance. We show that in contrast to control mice, those which lacked CXCR5 expression on CD11c+ cells failed to clear T. muris infection and developed cytokine and antibody responses that suggested a disturbed Th1/Th2 balance with enhanced IFN-γ expression. These data suggest an important role of CXCR5-expressing CD11c+ cells such as cDC in immunity to oral T. muris infection.

Keywords: Trichuris muris; CXCR5; Th2; dendritic cell; helminth; mucosal immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antibody Formation
  • B-Lymphocytes
  • CD11c Antigen / analysis*
  • Cytokines / analysis
  • Dendritic Cells / immunology
  • Disease Models, Animal
  • Disease Susceptibility
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, CXCR5 / analysis*
  • Specific Pathogen-Free Organisms
  • Th2 Cells / immunology
  • Trichuriasis / immunology*
  • Trichuriasis / parasitology
  • Trichuris / immunology*

Substances

  • CD11c Antigen
  • CXCR5 protein, mouse
  • Cytokines
  • Receptors, CXCR5