Increased susceptibility to oral Trichuris muris infection in the specific absence of CXCR5-expressing dendritic cells

Trichuris muris is a natural mouse helminth pathogen which establishes infection specifically in the caecum of the large intestine. The rapid expulsion of T. muris before the adult worms reach fecundity in resistant mouse strains is associated with the induction a protective T helper cell type 2 (Th2)-polarised immune response. In contrast, susceptible mouse strains mount an inappropriate Th1 response to T. muris infection which results in persistent infection. Expression of the chemokine CXCL13 by stromal follicular dendritic cells mediates the attraction of CXCR5-expressing cells towards and into the B cell follicles. Previous studies using a complex in vivo diphtheria-toxin mediated conventional dendritic cells (cDC) depletion model have suggested that CXCR5-expressing cDC help regulate the induction of Th2-polarized responses. In the current study, novel compound transgenic mice (CXCR5ΔDC) were used in which CXCR5-deficiency was specifically restricted to CD11c+ mononuclear phagocytes. This line was estanlished by cross-breeding conditional CXCR5 mice (CXCR5fl) with the CD11c-Cre transgenic mice. These mice were used to determine whether the specific absence CXCR5 on cDC would influence susceptibility to oral T. muris infection by affecting the Th1/Th2 balance. Our data show that in contrast to control mice, those which specifically lacked CXCR5-expressing cDC failed to clear T. muris infection. In the specific absence of CXCR5-expressing cDC the T. muris infected mice developed cytokine and antibody responses that suggested a disturbed Th1/Th2 balance and enhanced Th1 environment. These data suggest an important role for CXCR5-expressing cDC in immunity to oral T. muris infection.