Myeloid-Restricted AMPKα1 Promotes Host Immunity and Protects against IL-12/23p40-Dependent Lung Injury during Hookworm Infection

J Immunol. 2016 Jun 1;196(11):4632-40. doi: 10.4049/jimmunol.1502218. Epub 2016 Apr 20.


How the metabolic demand of parasitism affects immune-mediated resistance is poorly understood. Immunity against parasitic helminths requires M2 cells and IL-13, secreted by CD4(+) Th2 and group 2 innate lymphoid cells (ILC2), but whether certain metabolic enzymes control disease outcome has not been addressed. This study demonstrates that AMP-activated protein kinase (AMPK), a key driver of cellular energy, regulates type 2 immunity and restricts lung injury following hookworm infection. Mice with a selective deficiency in the AMPK catalytic α1 subunit in alveolar macrophages and conventional dendritic cells produced less IL-13 and CCL17 and had impaired expansion of ILC2 in damaged lung tissue compared with wild-type controls. Defective type 2 responses were marked by increased intestinal worm burdens, exacerbated lung injury, and increased production of IL-12/23p40, which, when neutralized, restored IL-13 production and improved lung recovery. Taken together, these data indicate that defective AMPK activity in myeloid cells negatively impacts type 2 responses through increased IL-12/23p40 production. These data support an emerging concept that myeloid cells and ILC2 can coordinately regulate tissue damage at mucosal sites through mechanisms dependent on metabolic enzyme function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / immunology*
  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Hookworm Infections / immunology*
  • Hookworm Infections / metabolism
  • Immunity, Innate / immunology*
  • Interleukin-12 / immunology*
  • Interleukin-23 / immunology*
  • Lung Injury / immunology*
  • Lung Injury / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Cells / immunology*
  • Myeloid Cells / metabolism


  • Interleukin-23
  • Interleukin-12
  • AMPK alpha1 subunit, mouse
  • AMP-Activated Protein Kinases