Tumour necrosis factor α restores granulomas and induces parasite egg-laying in schistosome-infected SCID mice

• Published in: Nature (London) 1992-04, Vol.356 (6370), p.604-607
• Main Authors: Amiri, Payman, Locksley, Richard M., Parslow, Tristram G., Sadickt, Michael, Rector, Ernest, Ritter, Dianne, McKerrow, James H.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal; Biological and medical sciences; Diseases caused by trematodes; Dose-Response Relationship, Drug; Female; Granuloma; Helminthic diseases; Humanities and Social Sciences; Immune Sera; Infectious diseases; Interleukin-4 - immunology; Interleukin-5 - immunology; letter; Liver - drug effects; Liver - parasitology; Liver - pathology; Lymphocyte Activation; Medical sciences; Mice; Mice, Inbred BALB C; Mice, SCID; multidisciplinary; Oviposition - drug effects; Parasitic diseases; Schistosoma mansoni; Schistosoma mansoni - physiology; Schistosomiases; Schistosomiasis mansoni - immunology; Schistosomiasis mansoni - parasitology; Schistosomiasis mansoni - pathology; Science; Science (multidisciplinary); Spleen - immunology; T-Lymphocytes - immunology; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/356604a0

SCHISTOSOMIASIS (bilharzia) is a parasitic disease caused by several species of schistosome worms (blood flukes). The key pathogenic event in this disease is the formation of granulomas around schistosome eggs trapped in portal venules of the liver 1–9 . Granulomas are a distinctive form of chronic inflammation characterized by localized aggregation of activated macrophages around an inciting stimulus 10 . Each granuloma evolves to form a fibrous scar; in schistosomiasis, the result is widespread hepatic fibrosis and portal hypertension. To identify the specific immune signal molecules necessary for granuloma formation, we studied schistosome infections in severe combined immunodeficient (SCID) mice, which have normal macrophages but lack functional B or T lymphocytes 11,12 . Here we report that the immunoregulatory cytokine tumour necrosis factor α is necessary and sufficient to reconstitute granuloma formation in schistosome-infected SCID mice. Moreover, we find that the parasitic worms require tumour necrosis factor α for egg-laying and for excretion of eggs from the host. The implication of this latter result is that the parasite has adapted so successfully to its host that it uses a host-derived immuno-regulatory protein as a signal for replication and transmission.