Hyperreactive onchocerciasis is characterized by a combination of Th17-Th2 immune responses and reduced regulatory T cells

PLoS Negl Trop Dis. 2015 Jan 8;9(1):e3414. doi: 10.1371/journal.pntd.0003414. eCollection 2015 Jan.

Abstract

Clinical manifestations in onchocerciasis range from generalized onchocerciasis (GEO) to the rare but severe hyperreactive (HO)/sowda form. Since disease pathogenesis is associated with host inflammatory reactions, we investigated whether Th17 responses could be related to aggravated pathology in HO. Using flow cytometry, filarial-specific cytokine responses and PCR arrays, we compared the immune cell profiles, including Th subsets, in individuals presenting the two polar forms of infection and endemic normals (EN). In addition to elevated frequencies of memory CD4+ T cells, individuals with HO showed accentuated Th17 and Th2 profiles but decreased CD4+CD25hiFoxp3+ regulatory T cells. These profiles included increased IL-17A+, IL-4+, RORC2+ and GATA3+CD4+ T cell populations. Flow cytometry data was further confirmed using a PCR array since Th17-related genes (IL-17 family members, IL-6, IL-1β and IL-22) and Th2-related (IL-4, IL-13, STAT6) genes were all significantly up-regulated in HO individuals. In addition, stronger Onchocerca volvulus-specific Th2 responses, especially IL-13, were observed in vitro in hyperreactive individuals when compared to GEO or EN groups. This study provides initial evidence that elevated frequencies of Th17 and Th2 cells form part of the immune network instigating the development of severe onchocerciasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Ghana / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Onchocerciasis / epidemiology
  • Onchocerciasis / immunology*
  • Onchocerciasis / pathology
  • T-Lymphocytes, Regulatory / physiology*
  • Th17 Cells / physiology*
  • Th2 Cells / physiology*
  • Young Adult

Grants and funding

This work was primarily supported through a grant from the German Research Council (DFG Ho2009/8-2). The study was further supported by the European Commission (grant No. 242121, EPIAF), the BONFOR intramural funding program of the Medical Faculty of Bonn University, and a European Foundation Initiative into African Research in Neglected Tropical diseases (EFINTD) awarded to AYD (grant 1/81995 and 86 52). GK and AK were supported by a fellowship awarded by the German Academic Exchange Committee (DAAD). LEL, AYD and AH are recipients of further DFG funding within the "African-German Cooperation Projects in Infectiology" (HO 2009/10-1). AH is a member of the Excellence Cluster Immunosensation (DFG, EXC 1023) and of the German Centre of Infectious Disease (DZIF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.