TH1-dominant granulomatous pathology does not inhibit fibrosis or cause lethality during murine schistosomiasis.
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.
Leeto
Mosiuoa
M
Division of Infectious Immunology, University of Cape Town, Cape Town, South Africa.
Herbert
De'Broski R
DR
Marillier
Reece
R
Schwegmann
Anita
A
Fick
Lizette
L
Brombacher
Frank
F
D000818:Animals; D000941:Antigens; D003094:Collagen / Q000378:metabolism; D004804:Eosinophils / Q000469:parasitology; D005355:Fibrosis / Q000276:immunology / Q000473:pathology; D041981:Gastrointestinal Tract / Q000469:parasitology; D015971:Gene Expression Regulation, Enzymologic; D020397:Goblet Cells / Q000469:parasitology; D006099:Granuloma / Q000276:immunology* / Q000473:pathology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008099:Liver / Q000166:cytology / Q000469:parasitology / Q000473:pathology*; D008168:Lung / Q000469:parasitology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D010063:Ovum; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019948:Receptors, Interleukin-4 / Q000172:deficiency; D012550:Schistosoma mansoni / Q000502:physiology; D012552:Schistosomiasis / Q000276:immunology* / Q000473:pathology*; D016019:Survival Analysis; D018417:Th1 Cells / Q000276:immunology*
D000941:Antigens; D012333:RNA, Messenger; D019948:Receptors, Interleukin-4; D007371:Interferon-gamma; D003094:Collagen; D052247:Nitric Oxide Synthase Type II