TH1-Dominant granulomatous pathology does not inhibit fibrosis or cause lethality during murine schistosomiasis

Schistosoma mansoni egg-induced inflammation is accompanied by T,2 cell polarization and development of fibrotic granulomas in host tissue. The interleukin (IL)-4 receptor alpha (IEL-4R alpha), which mediates IL-4 and IL-13 signaling, is essential for granulomatous pathology through a putative CD4(+) T-cell-dependent mechanism. In this study, we asked whether CD4(+) T-cell-specific IEL-4R alpha-deficient mice (Lck(Cre)IL-4R alpha(-/lox)) developed granulomas and egg-driven collagen production. Although eosinophilia and goblet cell hyperplasia were impaired in Lck(Cre)IL-4R alpha(-/lox) mice, there was no reduction in size or collagen content of lung and liver granulomas. The lack of CD4(+) T-cell IL-4R alpha expression caused significant increases in interferon-gamma-producing cells, inducible nitric-oxide synthetase production, and hepatic damage, compared with similarly infected wild-type mice. interestingly, this T(H)1-associated liver injury did not lead to premature mortality in this strain. Instead, lower levels of serum endotoxin in Lck(Cre)IL-4R alpha(-/lox) mice suggest that intestinal barrier function may be the dominant factor for survival during natural infection.