Immunomodulatory effects of Eimeria maxima surface antigen (EmSAG) as an IFN-γ inhibitory molecule on peripheral blood mononuclear cells (PBMCs) and T cell subsets in chickens

巨型艾美球虫表面抗原(EmSAG)作为IFN-γ抑制分子对鸡外周血单核细胞(PBMC)和T细胞亚群的免疫调节作用

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Abstract

Eimeria maxima (E. maxima) infection inhibits the expression of IFN-γ, a cytokine that is essential for the Th1 immune response and plays a key role in combating this parasite. In our preliminary investigations, we identified the E. maxima surface antigen (EmSAG) as an inhibitory molecule of IFN-γ. EmSAG was screened and characterised from an E. maxima sporozoite cDNA expression library. The present study aimed to evaluate the immunomodulatory effects of EmSAG on chicken peripheral blood mononuclear cells (PBMCs) and various T cell subsets. We analysed cell proliferation, nitric oxide (NO) release, and cytokine transcription. The results revealed that EmSAG boosts PBMC proliferation and promotes differentiation of CD4(+)/CD8(+) T cells. Additionally, stimulation with EmSAG significantly inhibited NO release and IFN-γ transcription while enhancing the transcription of IL-4, IL-10, and TGF-β1 in chicken PBMCs. The sorting purity of T cell subsets was as follows: CD8(+) (96.90%), CD4(+) (86.25%), CD4(+)CD25(-) (89.14%), and CD4(+)CD25(+) regulatory T cells (Tregs; 92.16%). These purified subsets were co-incubated with EmSAG to analyse the transcription of hallmark cytokines associated with Th1, Th2, and Treg responses. EmSAG significantly inhibited the transcription of IFN-γ and IL-2 in both CD4(+) and CD8(+) T cells, while promoting the expression of IL-10, TGF-β1, and CTLA-4 in Tregs. Moreover, depletion of CD25(+) cells reversed the EmSAG-induced suppression of IL-2 transcription and reduced its stimulating effects on IL-4 and IL-10 transcription in CD4(+)CD25(-) T cells. These findings highlight the role of EmSAG as an inhibitor of IFN-γ, facilitating immune evasion by attenuating the Th1 immune response and modulating Treg cell function. This study provides critical insights into the immune evasion mechanisms utilised by chicken coccidia.

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