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

Abstract

Schistosoma mansoni egg-induced inflammation is accompanied by T H2 cell polarization and development of fibrotic granulomas in host tissue. The interleukin (IL)-4 receptor α (IL-4Rα), 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 IL-4Rα-deficient mice (Lck CreIL-4Rα-/lox) developed granulomas and egg-driven collagen production. Although eosinophilia and goblet cell hyperplasia were impaired in LckCreIL-4Rα-/lox mice, there was no reduction in size or collagen content of lung and liver granulomas. The lack of CD4+ T-cell IL-4Rα expression caused significant increases in interferon-γ-producing cells, inducible nitric-oxide synthetase production, and hepatic damage, compared with similarly infected wild-type mice. Interestingly, this TH1-associated liver injury did not lead to premature mortality in this strain. Instead, lower levels of serum endotoxin in LckCreIL-4Rα-/lox mice suggest that intestinal barrier function may be the dominant factor for survival during natural infection. Copyright © American Society for Investigative Pathology.