Th9 Cells Drive Host Immunity Against Gastrointestinal Worm Infection

Immunity. 2013 Oct 17;39(4):744-57. doi: 10.1016/j.immuni.2013.07.020.

Abstract

Type 2 inflammatory cytokines, including interleukin-4 (IL-4), IL-5, IL-9, and IL-13, drive the characteristic features of immunity against parasitic worms and allergens. Whether IL-9 serves an essential role in the initiation of host-protective responses is controversial, and the importance of IL-9- versus IL-4-producing CD4⁺ effector T cells in type 2 immunity is incompletely defined. Herein, we generated IL-9-deficient and IL-9-fluorescent reporter mice that demonstrated an essential role for this cytokine in the early type 2 immunity against Nippostrongylus brasiliensis. Whereas T helper 9 (Th9) cells and type 2 innate lymphoid cells (ILC2s) were major sources of infection-induced IL-9 production, the adoptive transfer of Th9 cells, but not Th2 cells, caused rapid worm expulsion, marked basophilia, and increased mast cell numbers in Rag2-deficient hosts. Taken together, our data show a critical and nonredundant role for Th9 cells and IL-9 in host-protective type 2 immunity against parasitic worm infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • Gene Expression Regulation
  • Immunity, Cellular*
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology
  • Interleukin-9 / deficiency
  • Interleukin-9 / genetics
  • Interleukin-9 / immunology*
  • Intestines / immunology*
  • Intestines / parasitology
  • Intestines / pathology
  • Lectins, C-Type / genetics
  • Lectins, C-Type / immunology*
  • Male
  • Mice
  • Mice, Knockout
  • Nippostrongylus / immunology*
  • Signal Transduction
  • Strongylida Infections / immunology*
  • Strongylida Infections / parasitology
  • Strongylida Infections / pathology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / parasitology
  • T-Lymphocytes, Helper-Inducer / pathology
  • T-Lymphocytes, Helper-Inducer / transplantation

Substances

  • DNA-Binding Proteins
  • Interleukin-9
  • Lectins, C-Type
  • MGL2 protein, mouse
  • Rag2 protein, mouse
  • Interleukin-4