Journal
JOURNAL OF IMMUNOLOGY
Volume 196, Issue 11, Pages 4632-4640Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1502218
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Funding
- National Institutes of Health [R01 A1095289, R01 GM83204]
- Burroughs Wellcome Fund Award [CA-0062619]
- National Institutes of Health Immunology Research Training Grant [2T32AI007334-16]
- Diversity Supplement Award
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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 alpha 1 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.
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