Intestinal helminth infection promotes IL-5- and CD4 + T cell-dependent immunity in the lung against migrating parasites

Mucosal Immunol. 2019 Mar;12(2):352-362. doi: 10.1038/s41385-018-0102-8. Epub 2018 Nov 6.

Abstract

The ability of helminths to manipulate the immune system of their hosts to ensure their own survival is often credited with affecting responses to other pathogens. We undertook co-infection experiments in mice to determine how infection with the intestinal helminth Heligmosomoides polygyrus affected the parasitological, immunological and physiological outcomes of a primary infection with a distinct species of helminth; the lung migratory parasite Nippostrongylus brasiliensis. We found that migrating N. brasiliensis larvae were killed in the lungs of H. polygyrus-infected mice by a process involving IL-33-activated CD4+ T cells that released IL-5 and recruited activated eosinophils. The lung pathology normally associated with N. brasiliensis larval migration was also reduced. Importantly, lung immunity remained intact in mice cleared of prior H. polygyrus infection and also occurred during infection with another entirely enteric helminth, Trichuris muris. This study identifies a cross-mucosal immune mechanism by which intestinal helminths may protect their hosts against co-infection by a different parasite at a distal site, via circulation of activated CD4+ T cells that can be triggered to release effector cytokines and mount inflammatory responses by tissue damage-associated alarmins, such as IL-33.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Helminth / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Movement
  • Cells, Cultured
  • Coinfection*
  • Cytotoxicity, Immunologic
  • Eosinophils / immunology*
  • Female
  • Host-Parasite Interactions
  • Immunity
  • Interleukin-33 / metabolism
  • Interleukin-5 / metabolism*
  • Lung / immunology*
  • Lung / parasitology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nematospiroides dubius / physiology*
  • Nippostrongylus / physiology*
  • Strongylida Infections / immunology*
  • Trichuriasis / immunology*
  • Trichuris / physiology*

Substances

  • Antigens, Helminth
  • Interleukin-33
  • Interleukin-5