How the immune system adapts to malnutrition to sustain immunity at barrier surfaces, such as the intestine, remains unclear. Vitamin A deficiency is one of the most common micronutrient deficiencies and is associated with profound defects in adaptive immunity. Here, we found that type 3 innate lymphoid cells (ILC3s) are severely diminished in vitamin A–deficient settings, which results in compromised immunity to acute bacterial infection. However, vitamin A deprivation paradoxically resulted in dramatic expansion of interleukin-13 (IL-13)–producing ILC2s and resistance to nematode infection in mice, which revealed that ILCs are primary sensors of dietary stress. Further, these data indicate that, during malnutrition, a switch to innate type 2 immunity may represent a powerful adaptation of the immune system to promote host survival in the face of ongoing barrier challenges.
An Immune Response to Malnutrition
Mucosal surfaces, such as those lining the intestine, are in constant contact with potentially pathogenic microbes, including bacteria and parasitic worms. This necessitates so-called barrier immunity, which is mediated in part by innate lymphoid cells, subsets of which combat specific types of infection. Although malnutrition has been associated with immunosuppression, Spencer et al. (p. 432) now show that vitamin A deficiency selectively activates one branch of barrier immunity. Vitamin A deficiency in mice enhanced immunity to chronic worm infections by increasing the levels of one subset of innate lymphoid cells lacking the corresponding retinoic acid receptor. In contrast, another innate lymphoid cell subset that carries the vitamin A receptor and is important for bacterial immunity was depleted. Thus, the immune system can adapt its response to dietary stress, thereby promoting host survival.