title: Schistosome infection aggravates HCV-related liver disease and induces changes in the regulatory T-cell phenotype.
abstract: Schistosome infections are renowned for their ability to induce regulatory networks such as regulatory T cells (Treg) that control immune responses against homologous and heterologous antigens such as allergies. However, in the case of co-infections with hepatitis C virus (HCV), schistosomes accentuate disease progression and we hypothesized that expanding schistosome-induced Treg populations change their phenotype and could thereby suppress beneficial anti-HCV responses. We therefore analysed effector T cells and n/iTreg subsets applying the markers Granzyme B (GrzB) and Helios in Egyptian cohorts of HCV mono-infected (HCV), schistosome-co-infected (Sm/HCV) and infection-free individuals. Interestingly, viral load and liver transaminases were significantly elevated in Sm/HCV individuals when compared to HCV patients. Moreover, overall Treg frequencies and Helios(pos) Treg were not elevated in Sm/HCV individuals, but frequencies of GrzB(+) Treg were significantly increased. Simultaneously, GrzB(+) CD8(+) T cells were not suppressed in co-infected individuals. This study demonstrates that in Sm/HCV co-infected cohorts, liver disease is aggravated with enhanced virus replication and Treg do not expand but rather change their phenotype with GrzB possibly being a more reliable marker than Helios for iTreg. Therefore, curing concurrent schistosome disease could be an important prerequisite for successful HCV treatment as co-infected individuals respond poorly to interferon therapy.
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Loffredo-Verde
authors.forename: I
authors.initials: I
authors.lastname: Abdel-Aziz
authors.forename: J
authors.initials: J
authors.lastname: Albrecht
authors.forename: N
authors.initials: N
authors.lastname: El-Guindy
authors.forename: M
authors.initials: M
authors.lastname: Yacob
authors.forename: A
authors.initials: A
authors.lastname: Solieman
authors.forename: U
authors.initials: U
authors.lastname: Protzer
authors.forename: D H
authors.initials: DH
authors.lastname: Busch
authors.forename: L E
authors.initials: LE
authors.lastname: Layland
authors.forename: C U
authors.initials: CU
authors.lastname: Prazeres da Costa
mesh_terms: D000328:Adult; D000818:Animals; D060085:Coinfection / Q000276:immunology*; D005260:Female; D016174:Hepacivirus / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology; D008099:Liver / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D012550:Schistosoma mansoni / Q000502:physiology*; D012555:Schistosomiasis mansoni / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D019562:Viral Load
chemical_list: D016209:Interleukin-8
keywords: Granzyme B; Helios; Schistosoma mansoni; hepatitis C virus; liver disease; regulatory T cells