A STAT4-Dependent Th1 Response Is Required for Resistance to the Helminth ParasiteTaenia crassiceps

Abstract

To determine the role of STAT4-dependent Th1 responses in the regulation of immunity to the helminth parasiteTaenia crassiceps, we monitored infections with this parasite in resistant mice lacking the STAT4 gene. WhileT. crassiceps-infected STAT4^+/+mice rapidly resolved the infection, STAT4^−/−mice were highly susceptible to infection and displayed large parasite loads. Moreover, the inability of STAT4^−/−mice to control the infection was associated with the induction of an antigen-specific Th2-type response characterized by significantly higher levels of Th2-associated immunoglobulin G1 (IgG1) and total IgE as well as interleukin-4 (IL-4), IL-10, and IL-13 than those in STAT4^+/+mice, who produced significantly more gamma interferon. Furthermore, early after infection, macrophages from STAT4^−/−mice produced lower levels of the pro-inflammatory cytokines IL-12, tumor necrosis factor alpha, IL-1β, and nitric oxide (NO) than those from STAT4^+/+mice, suggesting a pivotal role for macrophages in mediating protection against cysticercosis. These findings demonstrate a critical role for the STAT4 signaling pathway in the development of a Th1-type immune response that is essential for mediating protection against the larval stage ofT. crassicepsinfection.