| Abstract | 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. |
| Authors | Mosiuoa Leeto, De'Broski R Herbert, Reece Marillier, Anita Schwegmann, Lizette Fick, Frank Brombacher
(Affiliation: Division of Infectious Immunology, University of Cape Town, Cape Town, South Africa.)
|
| Journal | The American journal of pathology
(Am J Pathol)
Vol. 169
Issue 5
Pg. 1701-12
(Nov 2006)
ISSN: 0002-9440 United States |
| PMID | 17071593
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Antigens
- RNA, Messenger
- Receptors, Interleukin-4
- Interferon-gamma
- Collagen
- Nitric Oxide Synthase Type II
|
| Topics |
- Animals
- Antigens
- Collagen
(metabolism)
- Eosinophils
(parasitology)
- Fibrosis
(immunology, pathology)
- Gastrointestinal Tract
(parasitology)
- Gene Expression Regulation, Enzymologic
- Goblet Cells
(parasitology)
- Granuloma
(immunology, pathology)
- Interferon-gamma
(biosynthesis)
- Liver
(cytology, parasitology, pathology)
- Lung
(parasitology, pathology)
- Mice
- Mice, Inbred BALB C
- Nitric Oxide Synthase Type II
(genetics)
- Ovum
- RNA, Messenger
(genetics, metabolism)
- Receptors, Interleukin-4
(deficiency)
- Schistosoma mansoni
(physiology)
- Schistosomiasis
(immunology, pathology)
- Survival Analysis
- Th1 Cells
(immunology)
|
