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

Katawa G, Layland LE, Debrah AY, von Horn C, Batsa L, Kwarteng A, Arriens S, W Taylor D, Specht S, Hoerauf A, Adjobimey T - PLoS Negl Trop Dis (2015)

Bottom Line: Since disease pathogenesis is associated with host inflammatory reactions, we investigated whether Th17 responses could be related to aggravated pathology in HO.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Hyperreactive individuals exhibit a dominant IL-4 and IL-17 phenotype.Isolated PBMCs from EN (n = 10) and O. volvulus-infected individuals presenting either GEO (n =  10) or HO (n = 6) were activated with a cell stimulation cocktail for 6 hours. Thereafter, cells were stained with an anti-CD4 antibody and after fixation and permeabilization further stained with anti-human antibodies specific for IFN-γ (A), IL-4 (B), IL-17A (C) and IL-10 (D). Intracellular cytokine expression was determined on the CD4+ T cell population by flow cytometry. Graphs show percentages as box whiskers (tukey) with outliers. Asterisks show statistical differences (Kruskal-Wallis and Mann Whitney test) between the groups indicated by the brackets (*p<0.05, **p<0.01, ***p<0.001).
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pntd-0003414-g002: Hyperreactive individuals exhibit a dominant IL-4 and IL-17 phenotype.Isolated PBMCs from EN (n = 10) and O. volvulus-infected individuals presenting either GEO (n =  10) or HO (n = 6) were activated with a cell stimulation cocktail for 6 hours. Thereafter, cells were stained with an anti-CD4 antibody and after fixation and permeabilization further stained with anti-human antibodies specific for IFN-γ (A), IL-4 (B), IL-17A (C) and IL-10 (D). Intracellular cytokine expression was determined on the CD4+ T cell population by flow cytometry. Graphs show percentages as box whiskers (tukey) with outliers. Asterisks show statistical differences (Kruskal-Wallis and Mann Whitney test) between the groups indicated by the brackets (*p<0.05, **p<0.01, ***p<0.001).

Mentions: Next, we determined the frequency of cytokine producing CD4+ T cells. CD4+IFN-γ+ T cells were significantly higher in EN when compared to either infected group (Fig. 2A). However, CD4+ T cells from GEO individuals did produce more IFN-γ than cells from HO individuals (Fig. 2A). In contrast, infected groups displayed significantly elevated frequencies of IL-4-secreting CD4+ T cells when compared to EN groups (Fig. 2B). Moreover, T cells from HO individuals produced more IL-4 than cells from GEO persons (Fig. 2B). Whereas IL-17A-producing CD4+ T cells appeared to be a unique characteristic in HO individuals (Fig. 2C), those with GEO had a dominant IL-10 phenotype (Fig. 2D).


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

Katawa G, Layland LE, Debrah AY, von Horn C, Batsa L, Kwarteng A, Arriens S, W Taylor D, Specht S, Hoerauf A, Adjobimey T - PLoS Negl Trop Dis (2015)

Hyperreactive individuals exhibit a dominant IL-4 and IL-17 phenotype.Isolated PBMCs from EN (n = 10) and O. volvulus-infected individuals presenting either GEO (n =  10) or HO (n = 6) were activated with a cell stimulation cocktail for 6 hours. Thereafter, cells were stained with an anti-CD4 antibody and after fixation and permeabilization further stained with anti-human antibodies specific for IFN-γ (A), IL-4 (B), IL-17A (C) and IL-10 (D). Intracellular cytokine expression was determined on the CD4+ T cell population by flow cytometry. Graphs show percentages as box whiskers (tukey) with outliers. Asterisks show statistical differences (Kruskal-Wallis and Mann Whitney test) between the groups indicated by the brackets (*p<0.05, **p<0.01, ***p<0.001).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4288720&req=5

pntd-0003414-g002: Hyperreactive individuals exhibit a dominant IL-4 and IL-17 phenotype.Isolated PBMCs from EN (n = 10) and O. volvulus-infected individuals presenting either GEO (n =  10) or HO (n = 6) were activated with a cell stimulation cocktail for 6 hours. Thereafter, cells were stained with an anti-CD4 antibody and after fixation and permeabilization further stained with anti-human antibodies specific for IFN-γ (A), IL-4 (B), IL-17A (C) and IL-10 (D). Intracellular cytokine expression was determined on the CD4+ T cell population by flow cytometry. Graphs show percentages as box whiskers (tukey) with outliers. Asterisks show statistical differences (Kruskal-Wallis and Mann Whitney test) between the groups indicated by the brackets (*p<0.05, **p<0.01, ***p<0.001).
Mentions: Next, we determined the frequency of cytokine producing CD4+ T cells. CD4+IFN-γ+ T cells were significantly higher in EN when compared to either infected group (Fig. 2A). However, CD4+ T cells from GEO individuals did produce more IFN-γ than cells from HO individuals (Fig. 2A). In contrast, infected groups displayed significantly elevated frequencies of IL-4-secreting CD4+ T cells when compared to EN groups (Fig. 2B). Moreover, T cells from HO individuals produced more IL-4 than cells from GEO persons (Fig. 2B). Whereas IL-17A-producing CD4+ T cells appeared to be a unique characteristic in HO individuals (Fig. 2C), those with GEO had a dominant IL-10 phenotype (Fig. 2D).

Bottom Line: Since disease pathogenesis is associated with host inflammatory reactions, we investigated whether Th17 responses could be related to aggravated pathology in HO.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus