Abstract
Summary 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.
Highlights
Mononuclear phagocytes (MNP) arise from precursors in the bone marrow and comprise a heterogeneous population of monocytes, conventional dendritic cells and tissue macrophages
The intestinal mucosa is populated by distinct MNP populations including MNP expressing the fractalkine receptor CX3CR1 and subsets of conventional dendritic cells (cDC) marked by differential expression of the integrins CD11b and CD103.1 The cDC are specialized antigen-presenting cells, and antigen presentation by cDC to uninfected cognate CD4+ T cells may induce T helper cell type 1 (Th1), Th2 or Th17 responses dependent on their subset.[2,3,4,5,6]
We have previously shown that in these mice, the Cre recombinase-mediated recombination of Cxcr[5] is restricted to CD11c+ cDC and that the migration of their cDC towards CXCL13 is impeded.[25]
Summary
Mononuclear phagocytes (MNP) arise from precursors in the bone marrow and comprise a heterogeneous population of monocytes, conventional dendritic cells (cDC) and tissue macrophages. Trichuris muris is a natural nematode parasite of mice whose larvae hatch in the caecum and proximal colon and invade the epithelium. Resistance to high-level infection with T. muris varies considerably between different conventional mouse strains. The rapid expulsion of T. muris before the adult worms reach
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