Antigenic dietary protein guides maturation of the host immune system promoting resistance to Leishmania major infection in C57BL/6 mice.

Abstract

The immature immune system requires constant stimulation by foreign antigens during the early stages of life to develop properly and to create efficient immune responses against later infections. We have previously shown that intake of antigenic dietary protein is critical for inducing maturation of the immune system as well as for the development of T helper type 1 (Th1) immunity. In this study, we show that administration of an amino acid (aa)-based diet during the development of the immune system subsequently resulted in inefficient control of Leishmania major infection in adult C57BL/6 mice. Compared with mice fed a control protein-containing diet, adult aa-fed mice showed a decreased interferon (IFN)-c response to parasite antigens and insufficient production of nitric oxide (NO), which is crucial to parasite death. However, no deviation towards Th2-specific immunity to L. major was observed. Phenotypic analysis of antigen-presenting cells (APCs) from aa-fed mice revealed deficient levels of the costimulatory molecules CD40 and CD80, and low levels of interleukin (IL)-12 produced by peritoneal macrophages, revealing an early stage of maturation of these cells. APCs isolated from aa-fed mice were unable to stimulate a Th1 response in vitro. Both phenotypic features of T cells from aa-fed mice and their ability to produce a Th1 response in the presence of mature APCs were unaffected when compared with T cells from control mice. The results presented here support the notion that regulation of Th1 immunity to infection includes environmental factors such as dietary proteins, which provide a natural source of stimulation that contributes to the process of maturation of APCs.