Location: Diet, Genomics and Immunology LaboratoryTitle: Adaptation of innate lymphoid cells to nutrient deprivation promotes type 2 barrier immunity Author
Submitted to: Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/15/2014
Publication Date: 1/24/2014
Citation: Spencer, S.P., Wilhelm, C., Yang, Q., Hall, J.A., Bouladoux, N., Boyd, A., Nutman, T.B., Urban Jr, J.F., Wang, J., Bhandoola, A., Ramalingam, T.R., Wynn, T.A., Belkaid, Y. 2014. Adaptation of innate lymphoid cells to nutrient deprivation promotes type 2 barrier immunity. Science. 343(6169):432-7. Interpretive Summary: A healthy intestinal barrier is required to absorb nutrients and exclude the entry of organisms that can cause disease. The immune system plays a role in affecting this balance as immune cells and protein products released by these cells contribute to immunity against micro-organisms like bacterial, but also macro-organisms like parasitic worms. The immune response to these two types of infections requires very different immune cells and protein products because of the differences in invasion of the intestinal barrier. This study shows a novel interaction between a specific micronutrient, vitamin A (VA), and the balance between development of immune cells that control bacterial versus parasitic worm infections. Diets fed to mice that were deficient in VA stimulated development of a population of innate lymphoid cells-2 (ILC2) that increased mucus production in the intestine and better controlled parasitic worm infection. In contrast, increasing the concentration of VA decreased the number of ILC2 and increased ILC3 cells that better control bacterial infection. These results suggest that immune cells can take cues from the diet and shift the potential to engage different types of infectious organisms. Dietary strategies to regulate the balance between these cell populations could be useful when there is potential for specific types of infection or as a therapeutic complement to more traditional ways of controlling infectious disease. Other scientists and clinicians who study and treat infections and related allergic disorders will benefit from these results.
Technical Abstract: Survival of the host relies on the establishment of site-specific barrier defense tailored to constrain pressures imposed by commensal and parasitic exposures. The host is confronted with the additional challenge of maintaining barrier immunity in fluctuating states of dietary availability, yet how the immune system adapts to the nutritional state of the host remains unclear. One major arm of barrier immunity is controlled by innate lymphoid cells (ILC) that localize to and defend epithelial surfaces. Here we show that the essential dietary nutrient vitamin A regulates an inverse balance between ILC subsets by promoting IL-22 producing ILC3 while directly suppressing IL-13 producing ILC2. Consequently, Vitamin A deficiency is associated with impaired immunity against bacterial infection and reciprocal increase in type 2 barrier responses and immunity to worm infection. These results reveal micronutrients as a novel instructive cue guiding ILC fate and demonstrate that RA acts as a keystone metabolite to control an ILC switch that supports barrier immunity. Further, these findings propose that, in settings of malnutrition, decreased levels of vitamin A promote the development of alternative, type 2 barrier responses to sustain host survival in the face of chronic mucosal challenges.