Dynamic, Helminth-Induced Immune Modulation Influences The Outcome Of Acute And Chronic Hepatitis B Virus Infection

Background. Chronic hepatitis B develops more frequently in countries with high prevalence of helminth infections. The crosstalk between these 2 major liver-residing pathogens, Schistosoma mansoni and hepatitis B virus (HBV), is barely understood.Methods. We used state-of-the-art models for both acute and chronic HBV infection to study the pathogen-crosstalk during the different immune phases of schistosome infection.Results. Although liver pathology caused by schistosome infection was not affected by either acute or chronic HBV infection, S mansoni infection influenced HBV infection outcomes in a phase-dependent manner. Interferon (IFN)-gamma secreting, HBV- and schistosome-specific CD8 T cells acted in synergy to reduce HBV-induced pathology during the T(H)1 phase and chronic phase of schistosomiasis. Consequently, HBV was completely rescued in IFN-gamma-deficient or in T(H)2 phase coinfected mice demonstrating the key role of this cytokine. It is interesting to note that secondary helminth infection on the basis of persistent (chronic) HBV infection increased HBV-specific T-cell frequency and resulted in suppression of virus replication but failed to fully restore T-cell function and eliminate HBV.Conclusions. Thus, schistosome-induced IFN-gamma had a prominent antiviral effect that outcompeted immunosuppressive effects of T(H)2 cytokines, whereas HBV coinfection did not alter schistosome pathogenicity.