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

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

Author information

1
Division of Experimental Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA 94110;
2
EPIRUS Biopharmaceuticals Netherlands BV, 3584 CM Utrecht, the Netherlands;
3
Institut National de la Santé et de la Recherché Médicale U1016, Institut Cochin, 75014 Paris, France; CNRS, UMR 8104, 75014 Paris, France; and Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France.
4
Division of Experimental Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA 94110; debroski@vet.upenn.edu.

Abstract

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.

PMID:
27183598
PMCID:
PMC4875814
DOI:
10.4049/jimmunol.1502218
[Indexed for MEDLINE]
Free PMC Article

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