Conditional IL-4/IL-13-deficient mice reveal a critical role of innate immune cells for protective immunity against gastrointestinal helminths

Mucosal Immunol. 2015 May;8(3):672-82. doi: 10.1038/mi.2014.101. Epub 2014 Oct 22.


Approximately one-third of the world population is infected with gastrointestinal helminths. Studies in mouse models have demonstrated that the cytokines interleukin (IL)-4 and IL-13 are essential for worm expulsion, but the critical cellular source of these cytokines is poorly defined. Here, we compared the immune response to Nippostrongylus brasiliensis in wild-type, T cell-specific IL-4/IL-13-deficient and general IL-4/IL-13-deficient mice. We show that T cell-derived IL-4/IL-13 promoted T helper 2 (Th2) polarization in a paracrine manner, differentiation of alternatively activated macrophages, and tissue recruitment of innate effector cells. However, innate IL-4/IL-13 played the critical role for induction of goblet cell hyperplasia and secretion of effector molecules like Mucin5ac and RELMβ in the small intestine. Surprisingly, T cell-specific IL-4/IL-13-deficient and wild-type mice cleared the parasite with comparable efficiency, whereas IL-4/IL-13-deficient mice showed impaired expulsion. These findings demonstrate that IL-4/IL-13 produced by cells of the innate immune system is required and sufficient to initiate effective type 2 immune responses resulting in protective immunity against N. brasiliensis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Gene Expression Regulation
  • Goblet Cells / immunology
  • Goblet Cells / parasitology
  • Hormones, Ectopic / genetics
  • Hormones, Ectopic / immunology
  • Immunity, Innate*
  • Immunity, Mucosal*
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-13 / deficiency
  • Interleukin-13 / genetics
  • Interleukin-13 / immunology*
  • Interleukin-4 / deficiency
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology*
  • Macrophage Activation
  • Macrophages / immunology
  • Macrophages / parasitology
  • Mice
  • Mice, Knockout
  • Mucins / genetics
  • Mucins / immunology
  • Nippostrongylus / immunology*
  • Paracrine Communication
  • Signal Transduction
  • Strongylida Infections / immunology*
  • Strongylida Infections / parasitology
  • Strongylida Infections / pathology
  • Th2 Cells / immunology
  • Th2 Cells / parasitology


  • Hormones, Ectopic
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-13
  • Mucins
  • Retnlb protein, mouse
  • Interleukin-4