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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 onchocerciasis individuals present higher frequencies of CD4+Foxp3+ but not CD4+CD25hiFoxp3+ T cells.PBMCs from EN and O. volvulus-infected GEO or HO individuals were activated with a cell stimulation cocktail for 6 hours. Thereafter, cells were stained for CD4 and the transcription factors T-bet (A) or Foxp3 (B). PBMCs fractions were also stained with CD25 to assess the numbers of CD4+CD25hi (C) and CD4+CD25hiFoxp3+ (D) T cells in each individual (EN n = 16, GEO n =  16, HO n =  6). Cell population frequencies were determined via 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-g003: Hyperreactive onchocerciasis individuals present higher frequencies of CD4+Foxp3+ but not CD4+CD25hiFoxp3+ T cells.PBMCs from EN and O. volvulus-infected GEO or HO individuals were activated with a cell stimulation cocktail for 6 hours. Thereafter, cells were stained for CD4 and the transcription factors T-bet (A) or Foxp3 (B). PBMCs fractions were also stained with CD25 to assess the numbers of CD4+CD25hi (C) and CD4+CD25hiFoxp3+ (D) T cells in each individual (EN n = 16, GEO n =  16, HO n =  6). Cell population frequencies were determined via 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: In association with their elevated numbers of IFN-γ-producing CD4+ T cells (Fig. 2A), EN had significantly higher frequencies of CD4+T-bet+ T cells when compared to HO individuals (Fig. 3A). Strikingly, the Treg associated transcription factor Foxp3 was strongly expressed by CD4+ T cells from hyperreactive individuals, even when compared to GEO individuals (Fig. 3B). Therefore, we expanded our profile panel to include CD25hi expressing CD4+ T cells using a previously described protocol and gating strategy [17], [18]. Interestingly, the inclusion of CD25hi cells dramatically changed the profile of CD4+ regulatory T cell profile in HO individuals since both CD4+CD25hi (Fig. 3C) and CD4+CD25hiFoxp3+ (Fig. 3D) subsets were higher in GEO individuals. This suggests the presence of Foxp3+ effector CD4+ T cells in persons with HO.


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 onchocerciasis individuals present higher frequencies of CD4+Foxp3+ but not CD4+CD25hiFoxp3+ T cells.PBMCs from EN and O. volvulus-infected GEO or HO individuals were activated with a cell stimulation cocktail for 6 hours. Thereafter, cells were stained for CD4 and the transcription factors T-bet (A) or Foxp3 (B). PBMCs fractions were also stained with CD25 to assess the numbers of CD4+CD25hi (C) and CD4+CD25hiFoxp3+ (D) T cells in each individual (EN n = 16, GEO n =  16, HO n =  6). Cell population frequencies were determined via 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

License
Show All Figures
getmorefigures.php?uid=PMC4288720&req=5

pntd-0003414-g003: Hyperreactive onchocerciasis individuals present higher frequencies of CD4+Foxp3+ but not CD4+CD25hiFoxp3+ T cells.PBMCs from EN and O. volvulus-infected GEO or HO individuals were activated with a cell stimulation cocktail for 6 hours. Thereafter, cells were stained for CD4 and the transcription factors T-bet (A) or Foxp3 (B). PBMCs fractions were also stained with CD25 to assess the numbers of CD4+CD25hi (C) and CD4+CD25hiFoxp3+ (D) T cells in each individual (EN n = 16, GEO n =  16, HO n =  6). Cell population frequencies were determined via 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: In association with their elevated numbers of IFN-γ-producing CD4+ T cells (Fig. 2A), EN had significantly higher frequencies of CD4+T-bet+ T cells when compared to HO individuals (Fig. 3A). Strikingly, the Treg associated transcription factor Foxp3 was strongly expressed by CD4+ T cells from hyperreactive individuals, even when compared to GEO individuals (Fig. 3B). Therefore, we expanded our profile panel to include CD25hi expressing CD4+ T cells using a previously described protocol and gating strategy [17], [18]. Interestingly, the inclusion of CD25hi cells dramatically changed the profile of CD4+ regulatory T cell profile in HO individuals since both CD4+CD25hi (Fig. 3C) and CD4+CD25hiFoxp3+ (Fig. 3D) subsets were higher in GEO individuals. This suggests the presence of Foxp3+ effector CD4+ T cells in persons with HO.

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