Myeloid-Restricted AMPKα1 Promotes Host Immunity and Protects against IL-12/23p40-Dependent Lung Injury during Hookworm Infection.
Wildaliz NievesLi-Yin HungTaylor K OniskeyLouis BoonMarc ForetzBenoit ViolletDe'Broski R HerbertPublished in: Journal of immunology (Baltimore, Md. : 1950) (2016)
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.
Keyphrases
- induced apoptosis
- protein kinase
- dendritic cells
- cell cycle arrest
- skeletal muscle
- wild type
- bone marrow
- acute myeloid leukemia
- oxidative stress
- endoplasmic reticulum stress
- immune response
- type diabetes
- metabolic syndrome
- cell proliferation
- machine learning
- big data
- adipose tissue
- cell death
- insulin resistance
- replacement therapy
- ulcerative colitis
- deep learning
- high fat diet induced