Secondary alveolar echinococcosis in lymphotoxin-alpha and tumour necrosisfactor-alpha 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 necrosi s factor (TNF)-alpha genes enabled us to investigate the role of the the TN F during alveolar echinococcosis. We compared the growth rate of Echinococc us multilocularis in LT-alpha TNF-alpha +/+ mice to that of mice having eit her no or only one LT-alpha TNF-alpha functionnal allele. LT-alpha TNF-alph a -/- mice harboured a significantly higher parasite burden than did the ot her two populations at 5, 10, and 15 weeks of infection, and they did not s urvive thereafter. Liver metacestodes removed St-om these mice weve alive a nd 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 lead ing to focal liver fibrosis at an early stage of infection. In contrast, mo st 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 c haracteristics intermediate between homozygous mutants and wild-type mice. Levels of E. multilocularis-specific delayed-type hypersensitivity and seru m antibodies were slightly decreased in LT-alpha TNF-alpha -/- mice, This s tudy 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 i nfection.