Schistosome infection aggravates HCV-related liver disease and induces changes in the regulatory T-cell phenotype

Parasite Immunol. 2015 Feb;37(2):97-104. doi: 10.1111/pim.12171.

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.

Keywords: Granzyme B; Helios; Schistosoma mansoni; hepatitis C virus; liver disease; regulatory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Coinfection / immunology*
  • Female
  • Hepacivirus / physiology*
  • Hepatitis C, Chronic / immunology*
  • Humans
  • Interleukin-8 / immunology
  • Liver / pathology
  • Liver / virology
  • Male
  • Middle Aged
  • Schistosoma mansoni / physiology*
  • Schistosomiasis mansoni / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Viral Load

Substances

  • Interleukin-8