The role of IL-4, IL-13 and IL-4Rα in the development of protective and pathological responses to Trichinella spiralis

T helper type 2 (Th2) responses have been shown to be important in protective responses to gastrointestinal (GI) helminth infections and in the development of the intestinal pathology accompanying expulsion of the parasite. Different inbred mouse strains have been shown to develop different cytokine profiles following infection with GI helminths with increased resistance observed in those strains where Th2 cytokines predominate. The aim of this study was to determine the role of IL-4, IL-13 and IL-4Rα and the impact of host background on the development of the protective and pathological responses induced by infection with the gastrointestinal helminth Trichinella spiralis. IL-4, IL-13 and IL-4Rα were required for the generation of Th2 responses to T. spiralis; however, the role these responses play in the development of protection and enteropathy was less clear. IL-4Rα-deficiency mice resulted in substantially reduced parasite expulsion, intestinal pathology and Th2 responses. Similarly, lack of IL-13 resulted in inhibited expulsion and the development of enteropathy. Although Th2 responses were reduced in BALB/c IL-4–/– mice, neither expulsion nor enteropathy were different from wild-type mice. In contrast, C57BL/6 IL-4–/– exhibited delayed expulsion and reduced pathology, suggesting that host genetics are important in the function of individual cytokines. Thus, differences in background genotype may be an important component in the development host protection and the development of intestinal pathology accompanying the loss of GI helminths

Immunity to the model intestinal helminth parasite Heligmosomoides polygyrus

Heligmosomoides polygyrus is a natural intestinal parasite of mice, which offers an excellent model of the immunology of gastrointestinal helminth infections of humans and livestock. It is able to establish long-term chronic infections in many strains of mice, exerting potent immunomodulatory effects that dampen both protective immunity and bystander reactions to allergens and autoantigens. Immunity to the parasite develops naturally in some mouse strains and can be induced in others through immunization; while the mechanisms of protective immunity are not yet fully defined, both antibodies and a host cellular component are required, with strongest evidence for a role of alternatively activated macrophages. We discuss the balance between resistance and susceptibility in this model system and highlight new themes in innate and adaptive immunity, immunomodulation, and regulation of responsiveness in helminth infection