TH1-Dominant Granulomatous Pathology Does Not Inhibit Fibrosis or Cause Lethality during Murine Schistosomiasis

• Published in: The American journal of pathology Vol. 169; no. 5; pp. 1701 - 1712
• Main Authors: Leeto, Mosiuoa, Herbert, De'Broski R, Marillier, Reece, Schwegmann, Anita, Fick, Lizette, Brombacher, Frank
• Format: Journal Article
• Language: English
• Published: Bethesda, MD ASIP 01.11.2006; American Society for Investigative Pathology
• Subjects: Animals; Antigens; Biological and medical sciences; Collagen - metabolism; Diseases caused by trematodes; Eosinophils - parasitology; Fibrosis - immunology; Fibrosis - pathology; Gastrointestinal Tract - parasitology; Gene Expression Regulation, Enzymologic; Goblet Cells - parasitology; Granuloma - immunology; Granuloma - pathology; Helminthic diseases; Infectious diseases; Interferon-gamma - biosynthesis; Investigative techniques, diagnostic techniques (general aspects); Liver - cytology; Liver - parasitology; Liver - pathology; Lung - parasitology; Lung - pathology; Medical sciences; Mice; Mice, Inbred BALB C; Nitric Oxide Synthase Type II - genetics; Ovum; Parasitic diseases; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Receptors, Interleukin-4 - deficiency; Regular; RNA, Messenger - genetics; RNA, Messenger - metabolism; Schistosoma mansoni - physiology; Schistosomiases; Schistosomiasis - immunology; Schistosomiasis - pathology; Survival Analysis; Th1 Cells - immunology; Rodentia; Trematode disease; Th1 lymphocyte; Parasitosis; Helminthiasis; Infection; Schistosomiasis; Vertebrata; Anatomic pathology; Mammalia; Mouse; Animal; Fibrosis; T-Lymphocyte; Inhibitor
• ISSN: 0002-9440; 1525-2191
• DOI: 10.2353/ajpath.2006.060346

Schistosoma mansoni egg-induced inflammation is accompanied by TH2 cell polarization and development of fibrotic granulomas in host tissue. The interleukin (IL)-4 receptor alpha (IL-4Ralpha), 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-4Ralpha-deficient mice (Lck(Cre)IL-4Ralpha(-/lox)) developed granulomas and egg-driven collagen production. Although eosinophilia and goblet cell hyperplasia were impaired in Lck(Cre)IL-4Ralpha(-/lox) mice, there was no reduction in size or collagen content of lung and liver granulomas. The lack of CD4+ T-cell IL-4Ralpha 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 TH1-associated liver injury did not lead to premature mortality in this strain. Instead, lower levels of serum endotoxin in Lck(Cre)IL-4Ralpha(-/lox) mice suggest that intestinal barrier function may be the dominant factor for survival during natural infection.