Functional specialization of intestinal dendritic cell subsets during Th2 helminth infection in mice

Eur J Immunol. 2018 Jan;48(1):87-98. doi: 10.1002/eji.201747073. Epub 2017 Nov 2.

Abstract

Dendritic cells (DCs) are essential in dictating the nature and effectiveness of immune responses. In the intestine DCs can be separated into discrete subsets, defined by expression of CD11b and CD103, each with different developmental requirements and distinct functional potential. Recent evidence has shown that different intestinal DC subsets are involved in the induction of T helper (Th)17 and regulatory T cell responses, but the cells that initiate Th2 immune responses are still incompletely understood. We show that in the Th2 response to an intestinal helminth in mice, only CD11b+ and not CD11b- DCs accumulate in the local lymph node, upregulate PDL2 and express markers of alternative activation. An enteric Th1 response instead activated both CD11b+ and CD11b- DCs without eliciting alternative activation in either population. Functionally, only CD11b+ DCs activated during helminth infection supported Th2 differentiation in naive CD4+ T cells. Together our data demonstrate that the ability to prime Th2 cells during intestinal helminth infection, is a selective and inducible characteristic of CD11b+ DCs.

Keywords: Alternative activation; CD11b+ dendritic cells; Helminth infection; Programmed Death-Ligand 2; Th2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • CD11b Antigen / metabolism
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Dendritic Cells / classification
  • Dendritic Cells / immunology*
  • Integrin alpha Chains / metabolism
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / parasitology
  • Intestine, Small / cytology
  • Intestine, Small / immunology
  • Intestine, Small / parasitology
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nematospiroides dubius / immunology*
  • Receptors, Cell Surface / immunology
  • Strongylida Infections / immunology*
  • Strongylida Infections / parasitology
  • Th1 Cells / immunology
  • Th2 Cells / immunology*

Substances

  • Antigens, CD
  • CD11b Antigen
  • Il4ra protein, mouse
  • Integrin alpha Chains
  • Receptors, Cell Surface
  • alpha E integrins