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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
Author(s) -
Amiot Franck,
Vuong Phat,
Defontaines Marie,
Pater Clotilde,
Dautry François,
Liance Martine
Publication year - 1999
Publication title -
parasite immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 75
eISSN - 1365-3024
pISSN - 0141-9838
DOI - 10.1046/j.1365-3024.1999.00245.x
Subject(s) - echinococcus multilocularis , lymphotoxin , biology , alpha (finance) , metacestode , exacerbation , granuloma , pathology , immunology , helminthiasis , eosinophilia , tumor necrosis factor alpha , necrosis , cestoda , echinococcosis , helminths , medicine , surgery , construct validity , patient satisfaction
The availability of mice carrying a deletion of LT‐α and tumour necrosis factor (TNF)‐α genes enabled us to investigate the role of the TNF during alveolar echinococcosis. We compared the growth rate of Echinococcus multilocularis in LT‐αTNF‐α +/+ mice to that of mice having either no or only one LT‐αTNF‐α functionnal allele. LT‐αTNF‐α−/− 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 from these mice were alive and the dehydrogenase activities of peritoneal metacestodes were decreased. Liver lesions regressed in most wild‐type mice. Indeed, dead parasites were cordoned by granulomas containing numerous macrophages and lymphocytes leading to focal liver fibrosis at an early stage of infection. In contrast, most of LT‐αTNF‐α−/− 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‐αTNF‐α−/− mice. This study shows that TNF‐α and/or LT‐α genes play an essential role in the immune protection mechanisms against E. multilocularis at the site of infection.