Protection against the early acute phase of Cryptosporidium parvum infection conferred by interleukin-4-induced expression of T helper 1 cytokines

Abstract

Immunity to Cryptosporidium parvum infection involves a T helper (Th) 1 response with interferon (IFN)-γ and interleukin (IL)-12 activity, but the role of Th2 cytokines, such as IL-4, is unclear. Around the peak of infection, production of oocysts in IL-4-deficient and IL-4 receptor α-deficient neonatal BALB/c mice was greater than that in wild-type (wt) mice. Susceptibility to infection was increased or decreased, respectively, in wt mice treated with anti-IL-4 neutralizing antibodies or recombinant IL-4. Excretion of oocysts by IFN-γ-deficient mice was unaffected by treatment with anti-IL-4, indicating that IL-4 stimulated IFN-γ activity. Early during infection, wt mice had increased intestinal expression of IFN-γ and IL-12 mRNA, compared with IL-4-deficient mice. Intestinal IL-4 was detected by Western blotting in wt mice 24 h after infection but not in uninfected control mice. These findings suggest that, early during C. parvum infection of BALB/c mice, there is production of IL-4 that promotes Th1-mediated immunity.