Immune response of mice infected with Schistosoma mansoni is modulated by antifibrotic treatment.

Abstract

Mice infected with Schistosoma mansoni treated with beta-aminopropionitrile (BAPN), an antifibrotic agent, and the antischistosomal drug praziquantel (PZQ) were resistant to challenge for up to 5 weeks post-treatment. The combined treatment resulted in profound changes to the liver granuloma cell matrix and the composition and function of the cellular infiltrate. Although granulocytes always predominated in the infiltrate, the proportion of the cells which were macrophages was higher in mice treated with BAPN alone (39.2%) than in infected mice which were untreated (15.2%) or treated with PZQ alone (12.4%), and much higher than in mice given the combined treatment (1.8%). Two products associated with macrophage activation and cytotoxicity [tumour necrosis factor-alpha (TNF-alpha) and nitric oxide] were only detected in mice harbouring a patent infection and there was a strong positive correlation between the concentrations of each. The relatively low TNF-alpha concentrations in BAPN-treated mice seemed to be associated with the relatively small granulomas observed in these mice. BAPN treatment also led to changes in the proliferative response of the treated mice's macrophages to mitogen and soluble schistosome-egg antigen and in spleen cellularity; these changes are probably associated with the resistance to challenge infection observed in mice given BAPN with PZQ. It is clear that BAPN treatment changes the dynamics of the delayed-type hypersensitivity response within the granuloma and that this impacts on other immunological sites. How this relates to the maintenance of post-treatment resistance to a challenge infection has still to be elucidated.