ILC2s and T cells cooperate to ensure maintenance of M2 macrophages for lung immunity against hookworms

Nat Commun. 2015 Apr 27;6:6970. doi: 10.1038/ncomms7970.

Abstract

Defining the immune mechanisms underlying protective immunity to helminth infection remains an important challenge. Here we report that lung CD4(+) T cells and Group 2 innate lymphoid cells (ILC2s) work in concert to block Nippostrongylus brasiliensis (Nb) development in the parenchyma within 48 h in mice. Immune-damaged larvae have a striking morphological defect that is dependent on the expansion of IL-13-producing ILC2 and CD4(+) T cells, and the activation of M2 macrophages. This T-cell requirement can be bypassed by administration of IL-2 or IL-33, resulting in expansion of IL-13-producing ILC2s and larval killing. Depletion of ILC2s inhibits larval killing in IL-2-treated mice. Our results broaden understanding of ILC2's role in immunity to helminths by demonstrating that they not only act as alarmin sensors, but can also be sustained by CD4(+) T cells, ensuring both the prompt activation and the maintenance of IL-13-dependent M2 macrophage immunity in the lung.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / physiology*
  • Host-Pathogen Interactions / immunology*
  • Interleukin-2 / metabolism
  • Interleukin-33 / metabolism
  • Lung / immunology*
  • Macrophages / physiology*
  • Mice, Inbred BALB C
  • Neutrophils / physiology
  • Nippostrongylus / physiology*
  • Rats, Inbred Lew

Substances

  • Il33 protein, mouse
  • Interleukin-2
  • Interleukin-33