Secondary alveolar echinococcosis in lymphotoxin-α and tumour necrosis factor-α deficient mice:: exacerbation of Echinococcus multilocularis larval growth is associated with cellular changes in the periparasitic granuloma

The availability of mice carrying a deletion of LT-alpha and tumour necrosis factor (TNF)-alpha genes enabled us to investigate the role of the the TNF during alveolar echinococcosis. We compared the growth rate of Echinococcus multilocularis in LT-alpha TNF-alpha +/+ mice to that of mice having either no or only one LT-alpha TNF-alpha functionnal allele. LT-alpha TNF-alpha -/- mice harboured a significantly higher parasite burden than did the other two populations at 5, 10, and 15 weeks of infection, and they did not survive thereafter. Liver metacestodes removed St-om these mice weve alive and the dehydrogenase activities of peritoneal metacestodes were decreased. Liver lesions regressed in most wild-type mice. Indeed, dead parasites were cordoned by granuloma containing numerous macrophages and lymphocytes leading to focal liver fibrosis at an early stage of infection. In contrast, most of LT-alpha TNF-alpha -/- mice harboured metacestodes interspersed with leucocytes, realising purulent abscesses with secondary extensive irregular fibrosis at a late stage of infection. Heterozygous mice had behavioural characteristics intermediate between homozygous mutants and wild-type mice. Levels of E. multilocularis-specific delayed-type hypersensitivity and serum antibodies were slightly decreased in LT-alpha TNF-alpha -/- mice, This study shows that TNF-alpha and/or LT-alpha genes play an essential role it? the immune protection mechanisms against E. multilocularis at the site of infection.