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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

Higher frequencies of monocytes and memory T cells in HO individuals.Isolated PBMCs from EN and individuals presenting either generalized (GEO) or hyperreactive onchocerciasis (HO) were stained with a combination of antibodies to determine the frequencies of CD8+ T cells (A); NK cells [CD3-CD16brightCD56dim (B) and CD3-CD16dimCD56bright (C)]; NKT cells [CD3+CD16+ (D) and CD3+CD56+ (E)]; CD19+CD27+ memory B cells (F); CD14+ monocytes (G); memory CD4+ T cells (H) and naive CD4+ T cells (I). Graphs show box whiskers (tukey) with outliers from EN n = 10, GEO n = 10 and HO n = 6. Asterisks show statistical differences (Kruskal-Wallis and Mann Whitney test) between the groups indicated by the brackets (*p<0.05, **p<0.01).
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pntd-0003414-g001: Higher frequencies of monocytes and memory T cells in HO individuals.Isolated PBMCs from EN and individuals presenting either generalized (GEO) or hyperreactive onchocerciasis (HO) were stained with a combination of antibodies to determine the frequencies of CD8+ T cells (A); NK cells [CD3-CD16brightCD56dim (B) and CD3-CD16dimCD56bright (C)]; NKT cells [CD3+CD16+ (D) and CD3+CD56+ (E)]; CD19+CD27+ memory B cells (F); CD14+ monocytes (G); memory CD4+ T cells (H) and naive CD4+ T cells (I). Graphs show box whiskers (tukey) with outliers from EN n = 10, GEO n = 10 and HO n = 6. Asterisks show statistical differences (Kruskal-Wallis and Mann Whitney test) between the groups indicated by the brackets (*p<0.05, **p<0.01).

Mentions: To distinguish differences in the immune cell profiles of individuals with onchocerciasis, we analyzed PBMCs for the frequency of innate and adaptive cell populations. Individuals with GEO had significantly less CD8+ T cells when compared to EN (Fig. 1A). When compared to levels in EN, both CD16brightCD56dim and CD16dimCD56brightNK populations were significantly lower in GEO and HO individuals but no differences could be observed between infected groups (Fig. 1B and C). CD3+CD16+ but not CD3+CD56+NKT cells were also lower in GEO but not HO individuals (Fig. 1D and 1E). Whereas no differences could be observed in the frequency of memory B cells (Fig. 1F), significantly elevated numbers of monocytes (CD14+ cells) were identified in HO individuals (Fig. 1G). When compared to GEO and EN groups, HO individuals displayed higher amounts of memory CD4+CD45RO+ (Fig. 1H) but significantly less naive T cells (Fig. 1I). These data were also reflected when calculated on absolute cell numbers.


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)

Higher frequencies of monocytes and memory T cells in HO individuals.Isolated PBMCs from EN and individuals presenting either generalized (GEO) or hyperreactive onchocerciasis (HO) were stained with a combination of antibodies to determine the frequencies of CD8+ T cells (A); NK cells [CD3-CD16brightCD56dim (B) and CD3-CD16dimCD56bright (C)]; NKT cells [CD3+CD16+ (D) and CD3+CD56+ (E)]; CD19+CD27+ memory B cells (F); CD14+ monocytes (G); memory CD4+ T cells (H) and naive CD4+ T cells (I). Graphs show box whiskers (tukey) with outliers from EN n = 10, GEO n = 10 and HO n = 6. Asterisks show statistical differences (Kruskal-Wallis and Mann Whitney test) between the groups indicated by the brackets (*p<0.05, **p<0.01).
© Copyright Policy
Related In: Results  -  Collection

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

pntd-0003414-g001: Higher frequencies of monocytes and memory T cells in HO individuals.Isolated PBMCs from EN and individuals presenting either generalized (GEO) or hyperreactive onchocerciasis (HO) were stained with a combination of antibodies to determine the frequencies of CD8+ T cells (A); NK cells [CD3-CD16brightCD56dim (B) and CD3-CD16dimCD56bright (C)]; NKT cells [CD3+CD16+ (D) and CD3+CD56+ (E)]; CD19+CD27+ memory B cells (F); CD14+ monocytes (G); memory CD4+ T cells (H) and naive CD4+ T cells (I). Graphs show box whiskers (tukey) with outliers from EN n = 10, GEO n = 10 and HO n = 6. Asterisks show statistical differences (Kruskal-Wallis and Mann Whitney test) between the groups indicated by the brackets (*p<0.05, **p<0.01).
Mentions: To distinguish differences in the immune cell profiles of individuals with onchocerciasis, we analyzed PBMCs for the frequency of innate and adaptive cell populations. Individuals with GEO had significantly less CD8+ T cells when compared to EN (Fig. 1A). When compared to levels in EN, both CD16brightCD56dim and CD16dimCD56brightNK populations were significantly lower in GEO and HO individuals but no differences could be observed between infected groups (Fig. 1B and C). CD3+CD16+ but not CD3+CD56+NKT cells were also lower in GEO but not HO individuals (Fig. 1D and 1E). Whereas no differences could be observed in the frequency of memory B cells (Fig. 1F), significantly elevated numbers of monocytes (CD14+ cells) were identified in HO individuals (Fig. 1G). When compared to GEO and EN groups, HO individuals displayed higher amounts of memory CD4+CD45RO+ (Fig. 1H) but significantly less naive T cells (Fig. 1I). These data were also reflected when calculated on absolute cell numbers.

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