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

• Published in: PLoS neglected tropical diseases Vol. 9; no. 1; p. e3414
• Main Authors: Katawa, Gnatoulma, Layland, Laura E, Debrah, Alex Y, von Horn, Charlotte, Batsa, Linda, Kwarteng, Alexander, Arriens, Sandra, W Taylor, David, Specht, Sabine, Hoerauf, Achim, Adjobimey, Tomabu
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.01.2015; Public Library of Science (PLoS)
• Subjects: Adult; Biology and Life Sciences; Comparative analysis; Cytokines; Development and progression; Disease; Female; Flow cytometry; Ghana - epidemiology; Health aspects; Humans; Immune response; Infections; Lymphocytes; Male; Medicine and Health Sciences; Middle Aged; Nematoda; Onchocerca volvulus; Onchocerciasis; Onchocerciasis - epidemiology; Onchocerciasis - immunology; Onchocerciasis - pathology; Pathology; Physiological aspects; Simulium; Skin diseases; Studies; T cells; T-Lymphocytes, Regulatory - physiology; Th17 Cells - physiology; Th2 Cells - physiology; Tropical diseases; Young Adult; Ghana; Africa
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0003414

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.