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(American Journal of Pathology. 2006;169:1701-1712.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.060346

T_H1-Dominant Granulomatous Pathology Does Not Inhibit Fibrosis or Cause Lethality during Murine Schistosomiasis

From the Division of Infectious Immunology, University of Cape Town, Cape Town, South Africa

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 (IL-4R), 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-4R-deficient mice (Lck^CreIL-4R^–/lox) developed granulomas and egg-driven collagen production. Although eosinophilia and goblet cell hyperplasia were impaired in Lck^CreIL-4R^–/lox mice, there was no reduction in size or collagen content of lung and liver granulomas. The lack of CD4⁺ T-cell IL-4R expression caused significant increases in interferon--producing cells, inducible nitric-oxide synthetase production, and hepatic damage, compared with similarly infected wild-type mice. Interestingly, this T_H1-associated liver injury did not lead to premature mortality in this strain. Instead, lower levels of serum endotoxin in Lck^CreIL-4R^–/lox mice suggest that intestinal barrier function may be the dominant factor for survival during natural infection.

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