The skin is an important bulwark of acquired immunity against intestinal helminths

J Exp Med. 2013 Nov 18;210(12):2583-95. doi: 10.1084/jem.20130761. Epub 2013 Oct 28.

Abstract

Once animals have experienced a helminthic infection, they often show stronger protective immunity against subsequent infections. Although helminthic infections are well known to elicit Th2-type immune responses, it remains ill-defined where and how acquired protection is executed. Here we show that skin-invading larvae of the intestinal helminth Nippostrongylus brasiliensis are surrounded by skin-infiltrating cells and are prevented from migrating out of infected skin during the second but not the first infection. B cell- or IgE receptor FcεRI-deficient mice showed impaired larval trapping in the skin. Selective ablation of basophils, but not mast cells, abolished the larval trapping, leading to increased worm burden in the lung and hence severe lung injury. Skin-infiltrating basophils produced IL-4 that in turn promoted the generation of M2-type macrophages, leading to the larval trapping in the skin through arginase-1 production. Basophils had no apparent contribution to worm expulsion from the intestine. This study thus reveals a novel mode of acquired antihelminth immunity, in which IgE-armed basophils mediate skin trapping of larvae, thereby limiting lung injury caused by larval migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • Antibodies, Helminth / biosynthesis
  • Arginase / genetics
  • Arginase / metabolism
  • Basophils / immunology
  • Basophils / parasitology
  • Intestinal Diseases, Parasitic / genetics
  • Intestinal Diseases, Parasitic / immunology*
  • Intestinal Diseases, Parasitic / parasitology
  • Larva / immunology
  • Lung Injury / immunology
  • Lung Injury / parasitology
  • Macrophages / classification
  • Macrophages / immunology
  • Macrophages / parasitology
  • Mast Cells / immunology
  • Mast Cells / parasitology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nippostrongylus / immunology*
  • Nippostrongylus / pathogenicity*
  • Parasite Load
  • Receptors, IgG / deficiency
  • Receptors, IgG / genetics
  • Receptors, IgG / metabolism
  • Skin / immunology*
  • Skin / parasitology*
  • Strongylida Infections / genetics
  • Strongylida Infections / immunology*
  • Strongylida Infections / parasitology

Substances

  • Antibodies, Helminth
  • Fcgr1 protein, mouse
  • Receptors, IgG
  • Arg1 protein, mouse
  • Arginase