title: Involvement of TNF in limiting liver pathology and promoting parasite survival during schistosome infection.
abstract: CD4(+) T cell responses and macrophage activation are essential components of schistosome egg-induced granuloma formation. Previous studies implicated tumour necrosis factor (TNF) as a potential mediator of macrophage recruitment and activation during schistosome infection. Here we demonstrate that signalling by TNF and its receptors can influence granuloma formation, but is ultimately dispensable for granuloma formation in this system. However, we identify a previously unrecognised role for TNF in limiting hepatocellular damage in response to schistosome eggs. Further, we show that this activity of TNF is independent of TNF receptors (TNFR1 and TNFR2). Taken together, these data suggest that additional, as yet unrecognised receptors exist for TNF and that these receptors are capable of mediating important pathological effects in the liver. Finally, we provide evidence that TNF plays an unexpected role in maintaining adult schistosome viability in the portal system.
authors.affiliation: Tropical Disease Research Unit, Department of Pathology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA. sdavies@cgl.ucsf.edu
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Davies
authors.forename: K C
authors.initials: KC
authors.lastname: Lim
authors.forename: Rebecca B
authors.initials: RB
authors.lastname: Blank
authors.forename: Jea-Hyoun
authors.initials: JH
authors.lastname: Kim
authors.forename: Kimberley D
authors.initials: KD
authors.lastname: Lucas
authors.forename: David C
authors.initials: DC
authors.lastname: Hernandez
authors.forename: Jonathon D
authors.initials: JD
authors.lastname: Sedgwick
authors.forename: James H
authors.initials: JH
authors.lastname: McKerrow
mesh_terms: D000818:Animals; D017209:Apoptosis; D004531:Eggs; D005260:Female; D008024:Ligands; D008099:Liver / Q000469:parasitology / Q000473:pathology*; D008102:Liver Circulation; D008109:Liver Diseases, Parasitic / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D012547:Schistosoma / Q000502:physiology; D012552:Schistosomiasis / Q000276:immunology / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D008024:Ligands; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha