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Recombinant Wolbachia surface protein (WSP)-induced T cell responses in Wuchereria bancrofti infections - PubMed

Recombinant Wolbachia surface protein (WSP)-induced T cell responses in Wuchereria bancrofti infections

C Shiny et al. Parasitol Res. 2012 Feb.

Abstract

Human lymphatic filariasis is a debilitating parasitic disease characterized by downregulation of the host's immune response in asymptomatic carriers along with profound hyperreactivity in chronic patients apart from putatively immune endemic normals. The endosymbiont Wolbachia, a bacterium of filarial nematodes has received much attention as possible chemotherapeutic target and its involvement in disease pathogenesis. The role of recombinant Wolbachia surface protein (rWSP), one of the most abundantly expressed proteins of the endosymbiont, in modulating cell-mediated immune responses in patients harboring Wuchereria bancrofti infections was evaluated in the current study. rWSP-induced lymphoproliferation with peripheral blood mononuclear cells suggested an impaired proliferative response in asymptomatic microfilaremic (MF) and symptomatic chronic pathology (CP) patients compared to endemic normals (EN). This was further supported by a significantly diminished expression of CD69 along with elevated levels of CD127 and CD62L in filarial patients (MF and CP) compared to EN. Further, rWSP induced the expression of regulatory T cell markers CTLA-4 and CD25 along with suppressor cytokines IL-10 and TGF-β in MF and CP patients compared to EN. However, the rWSP-stimulated expression of IFN-γ was diminished significantly in filarial patients compared to endemic normals. Thus, these findings suggest that WSP may also contribute to the suppression of immune responses seen in filarial patients.

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Figures

Fig. 1
Fig. 1

a rWSP-induced lymphoproliferation is not mediated by endotoxin contamination. PBMCs from endemic normals stimulated with rWSP in the presence or absence of polymyxin B sulfate. Horizontal bars indicate the geometric mean stimulation index for five samples, and error bars indicate standard deviation. b rWSP-induced lymphoproliferation in the PBMCs of the filarial patients. PBMCs stimulated with rWSP or BmA or PHA in filarial patients. The results are expressed as log10 values of stimulation index. The horizontal bars denote geometric mean of all the individuals in each group, and vertical bars denote mean±standard deviation. p values indicate *p= 0.01–0.05; **p=0.001–0.01

Fig. 2
Fig. 2

rWSP-induced expression of T cell activation markers in PBMCs of the filarial patients. Percentage of CD4+cells expressing T cell activation markers (CD69,CD62L,CD127) at the d basal level and after stimulation with a WSP, b BmA, c PHA in endemic normals (EN=10), microfilaremics (MF=5) and Chronic pathology (CP=10) group of individuals evaluated by flow cytometry. Each dot represents fold change over unstimulated controls (a, b, c) and expression levels (d) for each sample and horizontal bars indicate geometric mean. The differences between the groups are considered significant at p<0.05 and are represented by *p<0.05, **p<0.01, and ***p<0.001

Fig. 3
Fig. 3

rWSP-induced CTLA-4 and CD25 expression in CD4+ cells in PBMCs of the filarial patients. Percentage of CD4+ cells in PBMCs expressing CTLA-4 and CD25 at the d basal level and after stimulation with a WSP, b BmA, c PHA in endemic normals (EN=10), microfilaremics (MF=5), and chronic pathology (CP=10) group of individuals evaluated by flow cytometry. Each dot represents a fold change over unstimulated control (a, b, c) and expression levels (d) for each sample and horizontal bars indicate geometric mean. The differences between the groups are considered significant at p<0.05 and are represented by *p<0.05, **p<0.01, and ***p<0.001

Fig. 4
Fig. 4

rWSP-induced IFN-γ expression in PBMCs of the filarial patients. PBMC expression of IFN-γ mRNA as measured by real-time RT-PCR following 24-h stimulation with b WSP, c PHA or d BmA, and at the a basal level in endemic normals [EN] (n=10), microfilaremics [MF] (n=5) and [CP] (n=10) group of individuals. Results are depicted as net cytokine production or as fold change over unstimulated control. P values were calculated using the Mann– Whitney test. The differences between the groups are considered significant at p<0.05 and are represented by *p<0.05, **p<0.01, and ***p<0.001

Fig. 5
Fig. 5

rWSP-induced expression of IL-10 and TGF-β in PBMCs of the filarial patients. PBMC expression of IL-10 and TGF-β mRNA as measured by real-time RT-PCR following 24-h stimulation with a WSP, b BmA, c PHA, or and at the d basal level in EN (n=10), MF (n=5), and CP (n=10) group of individuals. Results are depicted as net cytokine production or as fold change over unstimulated control. P values were calculated using the Mann–Whitney test. The differences between the groups are considered significant at p<0.05 and are represented by *p<0.05, **p<0.01, and ***p<0.001

Fig. 6
Fig. 6

rWSP-induced secretion of suppressor cytokines IL-10 and TGF-β in filarial patients

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