title: Hyperreactive onchocerciasis is characterized by a combination of Th17-Th2 immune responses and reduced regulatory T cells.
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.
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany; Advanced School of Medical Biology and Food Technology (ESTBA), University of Lomé, Lomé, Togo.
authors.forename: Gnatoulma
authors.initials: G
authors.lastname: Katawa
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Layland
authors.affiliation: Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana; Faculty of Allied Health Sciences and School of Medical Sciences of Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
authors.forename: Alex Y
authors.initials: AY
authors.lastname: Debrah
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany.
authors.forename: Charlotte
authors.initials: C
authors.lastname: von Horn
authors.affiliation: Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana.
authors.forename: Linda
authors.initials: L
authors.lastname: Batsa
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kwarteng
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Arriens
authors.affiliation: Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, Scotland.
authors.forename: David
authors.initials: D
authors.lastname: W Taylor
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Specht
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Hoerauf
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany.
authors.forename: Tomabu
authors.initials: T
authors.lastname: Adjobimey
mesh_terms: D000328:Adult; D005260:Female; D005869:Ghana / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009855:Onchocerciasis / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D058504:Th17 Cells / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology*; D055815:Young Adult