Immunopathogenesis of schistosomiasis.
In schistosomiasis mansoni, the chronic egg-induced granulomatous response in the liver and intestines may eventually cause extensive tissue scarring and development of portal hypertension. Indeed, much of the morbidity and mortality associated with this disease is directly attributable to the deposition of connective tissue elements in affected tissues. Elucidating the mechanisms that regulate the severity of schistosomiasis has been a major research objective over the past several years. Research conducted with DNA microarrays as well as investigations with a variety of gene knock-out mice have been particularly helpful in achieving this goal. A notable accomplishment in the past few years was the identification of interleukin-13 (IL-13) and the IL-13 receptor complex as central regulators of disease progression in schistosomiasis. Liver fibrogenesis is severely decreased in infected IL-13-deficient mice as well as in wildtype animals treated with IL-13 antagonists. In contrast, IL-13 effector function increases dramatically in IL-13 receptor alpha2 (IL-13Ralpha2)-deficient mice. These mice develop severe hepatic fibrosis, fail to downregulate granuloma formation in the chronic phase of S. mansoni infection, and succumb to the disease at an accelerated rate; thus, identifying the 'decoy' IL-13 receptor as a critical life sustaining 'off' switch for tissue damaging egg-induced inflammation.
Wynn
Thomas A
TA
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. twynn@niaid.nih.gov
Thompson
Robert W
RW
Cheever
Allen W
AW
Mentink-Kane
Margaret M
MM
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000276:immunology / Q000469:parasitology / Q000503:physiopathology; D051379:Mice; D012550:Schistosoma mansoni / Q000254:growth & development / Q000472:pathogenicity*; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000503:physiopathology*; D018418:Th2 Cells / Q000378:metabolism*
D016207:Cytokines