Integrated analysis of innate, Th1, Th2, Th17, and regulatory cytokines identifies changes in immune polarisation following treatment of human schistosomiasis

J Infect Dis. 2013 Jul;208(1):159-69. doi: 10.1093/infdis/jis524. Epub 2012 Oct 8.

Abstract

Background: Schistosomiasis elicits cross-regulatory immune responses, but it is unclear how antihelminthic treatment affects this balance. This study integrates data on 13 cytokines elicited by 3 schistosome to examine how praziquantel treatment alters immune polarization and whether post-treatment cytokine profiles influence reinfection status.

Methods: Venous blood from 72 Schistosoma haematobium-exposed participants was cultured with schistosome egg, adult worm, and cercaria antigens pre- and 6 weeks post-praziquantel treatment. Innate inflammatory (tumor necrosis factor α [TNF-α], interleukin(IL-)-6, IL-8), Th1 (interferon γ [IFN-γ], IL-2, IL-12p70), Th2 (IL-4, IL-5, IL-13), Th17 (IL-17A, IL-21, IL-23p19), and regulatory (IL-10) cytokines were quantified via enzyme-linked immunosorbent assay. Cytokine data was integrated using nonmetric multidimensional scaling and factor analysis.

Results: Egg-specific cytokine phenotypes became more proinflammatory post-treatment due to increased TNF-α, IL-6, IL-8, IFN-γ, IL-12p70, and IL-23 levels. Post-treatment cercariae-specific responses were also more proinflammatory reflecting elevated IL-8. In contrast, post-treatment adult worm-specific responses were less inflammatory, reflecting lower post-treatment IL-6. A combination of egg-induced IL-6, IL-12p70, IL-21, and IL-23 and adult worm-induced IL-5 and IL-21 post-treatment was associated with reduced reinfection risk 18 months later.

Conclusions: Praziquantel treatment markedly alters polarization of schistosome-specific cytokine responses, and these changes, particularly in response to egg-stage parasites, may promote resistance to reinfection.

Keywords: Human; cytokine; helminth; immune response; praziquantel; schistosomiasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Anthelmintics / therapeutic use*
  • Child
  • Child, Preschool
  • Cytokines / blood
  • Cytokines / physiology*
  • Female
  • Humans
  • Immunity, Innate / immunology
  • Interferon-gamma / blood
  • Interleukin-10 / blood
  • Interleukin-12 / blood
  • Interleukin-13 / blood
  • Interleukin-17 / blood
  • Interleukin-2 / blood
  • Interleukin-23 / blood
  • Interleukin-4 / blood
  • Interleukin-5 / blood
  • Interleukin-6 / blood
  • Interleukin-8 / blood
  • Interleukins / blood
  • Male
  • Praziquantel / therapeutic use*
  • Schistosoma haematobium / immunology
  • Schistosomiasis / drug therapy
  • Schistosomiasis / immunology*
  • Schistosomiasis haematobia / drug therapy
  • Schistosomiasis haematobia / immunology*
  • Th1 Cells / immunology*
  • Th17 Cells / immunology*
  • Th2 Cells / immunology*
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Anthelmintics
  • Cytokines
  • Interleukin-13
  • Interleukin-17
  • Interleukin-2
  • Interleukin-23
  • Interleukin-5
  • Interleukin-6
  • Interleukin-8
  • Interleukins
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12
  • Interleukin-4
  • Praziquantel
  • Interferon-gamma
  • interleukin-21