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.