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Loffredo-Verde, E. ; Bhattacharjee, S.* ; Malo, A. ; Festag, J. ; Kosinska, A. ; Ringelhan, M.* ; Rim Sarkar, S.* ; Steiger, K.* ; Heikenwälder, M. ; Protzer, U. ; Prazeres da Costa, C.U.*

Dynamic, helminth-induced immune modulation influences the outcome of acute and chronic hepatitis B virus infection.

J. Infect. Dis. 221, 1448-1461 (2020)
Publ. Version/Full Text Research data DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Coinfection ; Hepatitis B ; Immunomodulation ; Liver ; Schistosoma Mansoni; Regulatory T-cells; C Virus; Schistosomiasis; Liver; Mice; Replication; Coinfection; Prevalence; Responses
ISSN (print) / ISBN 0022-1899
e-ISSN 1537-6613
Journal Journal of Infectious Diseases, The
Quellenangaben Volume: 221, Issue: 9, Pages: 1448-1461 Article Number: , Supplement: ,
Publisher Oxford University Press
Publishing Place Journals Dept, 2001 Evans Rd, Cary, Nc 27513 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Virology (VIRO)