Reciprocal immunomodulation in a schistosome and hepatotropic virus coinfection model.
Human coinfection with the helminth parasite Schistosoma mansoni and hepatitis B and hepatitis C viruses is associated with increased hepatic viral burdens and severe liver pathology. In this study we developed a murine S. mansoni/lymphocytic choriomeningitis virus (LCMV) coinfection model that reproduces the enhanced viral replication and liver pathology observed in human coinfections, and used this model to explore the mechanisms involved. Viral coinfection during the Th2-dominated granulomatous phase of the schistosome infection resulted in induction of a strong LCMV-specific T cell response, with infiltration of high numbers of LCMV-specific IFN-gamma-producing CD8+ cells into the liver. This was associated with suppression of production of the Th2 cytokines dominant during S. mansoni infection and a rapid increase in morbidity, linked to hepatotoxicity. Interestingly, the liver of coinfected mice was extremely susceptible to viral replication. This correlated with a reduced intrahepatic type I IFN response following virus infection. Schistosome egg Ags were found to suppress the type I IFN response induced in murine bone marrow-derived dendritic cells by polyinosinic-polycytidylic acid. These results suggest that suppression of the antiviral type I IFN response by schistosome egg Ags in vivo predisposes the liver to enhanced viral replication with ensuing immunopathological consequences, findings that may be paralleled in human schistosome/hepatotropic virus coinfections.
Edwards
Matthew J
MJ
Viral Immunology Group, The Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire, United Kingdom.
Buchatska
Olena
O
Ashton
Miranda
M
Montoya
Maria
M
Bickle
Quentin D
QD
Borrow
Persephone
P
D000818:Animals; D000947:Antigens, Helminth; D001117:Arenaviridae Infections / Q000150:complications* / Q000276:immunology* / Q000473:pathology / Q000821:virology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D006524:Hepatitis, Viral, Animal / Q000150:complications* / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis; D008099:Liver / Q000469:parasitology / Q000473:pathology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000472:pathogenicity / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010270:Parasite Egg Count; D012550:Schistosoma mansoni / Q000276:immunology / Q000302:isolation & purification; D012555:Schistosomiasis mansoni / Q000150:complications* / Q000276:immunology* / Q000469:parasitology; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors; D014779:Virus Replication
D000947:Antigens, Helminth; D016207:Cytokines; D007370:Interferon Type I