Location: Animal Parasitic Diseases LaboratoryTitle: Critical role of fatty acid metabolism in ILC2 mediated barrier protection during malnutrition and helminth infection
|WILHELM, C - National Institutes Of Health (NIH)|
|HARRISON, OJ - National Institutes Of Health (NIH)|
|SCHMITT, V - University Of Bonn|
|PELLETIER, M - National Institutes Of Health (NIH)|
|SPENCER, SP - National Institutes Of Health (NIH)|
|PLOCH, M - National Institutes Of Health (NIH)|
|RAMALINGAM, TR - National Institutes Of Health (NIH)|
|SIEGEL, RM - National Institutes Of Health (NIH)|
|BELKAID, Y. - National Institutes Of Health (NIH)|
Submitted to: Journal of Experimental Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/18/2016
Publication Date: 7/25/2016
Citation: Wilhelm, C., Harrison, O., Schmitt, V., Pelletier, M., Spencer, S., Urban Jr, J.F., Ploch, M., Ramalingam, T., Siegel, R., Belkaid, Y. 2016. Critical role of fatty acid metabolism in ILC2 mediated barrier protection during malnutrition and helminth infection. Journal of Experimental Medicine. 213(8):1409-1418. doi: 10.1084/jem.20151448.
Interpretive Summary: Helminth (worm) infections are a global health concern in humans as well as livestock because they establish chronic and repeated infections. There is a population of cells called innate lymphoid cell 2 (ILC2) that expand during worm infection and contribute to a more vigorous protective response. These cells also regulate the barrier function of the intestine to prevent bacterial invasion. Vitamin A deficiency is one of the most common and severe nutrient deficiencies, and is characterized by a paradoxical increase in ILC2 that allows the host to sustain barrier immunity and to maintain responses to worms in the face of malnutrition. ILC2s adapt to vitamin A deficiency by increased use of certain dietary fatty acids. This report revealed how ILC2 adapt to nutritional challenges to sustain protective barrier function by altering fatty acid metabolism. This information will be of interest to scientists interested in developing useful and safe procedures to protect humans and livestock from parasitic infection and allergic disease especially under conditions of nutrient limitations.
Technical Abstract: Innate lymphoid cells (ILCs) play an important role in many immune processes, including control of infections, inflammation and tissue repair. To date little is known about the metabolism of ILCs under steady-state conditions and infection, and whether these cells can metabolically adapt in response to environmental signals. Here we show that type 2 innate lymphoid cells (ILC2), important mediators of barrier immunity, predominantly depend on fatty acid (FA) metabolism during helminth infection. In situations where an essential nutrient, such as vitamin A, is limited, ILC2 sustain their function and maintain barrier integrity via increased acquisition and utilization of FA. Under these conditions, ILC2 selectively maintain IL-13 expression. Together, these results reveal that ILC2 preferentially utilize fatty acids to maintain barrier immunity in the context of helminth infection or malnutrition and propose that enhanced FA usage and FA dependent IL-13 production by ILC2 could represent a host adaptation to maintain barrier immunity under dietary restriction.