Eosinophils are required to suppress Th2 responses in Peyer's patches during intestinal infection by nematodes

Mucosal Immunol. 2017 May;10(3):661-672. doi: 10.1038/mi.2016.93. Epub 2016 Nov 2.

Abstract

Infections with enteric nematodes result in systemic type 2 helper T (Th2) responses, expansion of immunoglobulin (Ig)G1 antibodies, and eosinophilia. Eosinophils have a supportive role in mucosal Th2 induction during airway hyperreactivity. Whether eosinophils affect the local T-cell and antibody response in the gut-associated lymphoid tissue during enteric infections is unknown. We infected eosinophil-deficient ΔdblGATA-1 mice with the Th2-inducing small intestinal nematode Heligmosomoides polygyrus and found that parasite fecundity was decreased in the absence of eosinophils. A lack of eosinophils resulted in significantly augmented expression of GATA-3 and IL-4 by CD4+ T cells during acute infection, a finding strictly limited to Peyer's patches (PP). The increase in IL-4-producing cells in ΔdblGATA-1 mice was particularly evident within the CXCR5+PD-1+ T-follicular helper cell population and was associated with a switch of germinal centre B cells to IgG1 production and elevated serum IgG1 levels. In contrast, infected wild-type mice had a modest IgG1 response in the PP, whereas successfully maintaining a population of IgA+ germinal center B cells. Our results suggest a novel role for eosinophils during intestinal infection whereby they restrict IL-4 responses by follicular T helper cells and IgG1 class switching in the PP to ensure maintenance of local IgA production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Cells, Cultured
  • Eosinophils / immunology*
  • Eosinophils / parasitology
  • Female
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / metabolism
  • Immune Tolerance
  • Immunoglobulin A / metabolism
  • Immunoglobulin G / metabolism
  • Interleukin-4 / metabolism
  • Intestines / immunology*
  • Intestines / parasitology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nematospiroides dubius / immunology*
  • Peyer's Patches / immunology*
  • Strongylida Infections / immunology*
  • Th2 Cells / immunology*

Substances

  • GATA3 Transcription Factor
  • Immunoglobulin A
  • Immunoglobulin G
  • Interleukin-4