Depletion of CD25cells restores Th1, Th2 and Th17 responses and mitigates Eimeria maxima infection in chickens.

Abstract

Chicken coccidia can suppress the host immune response through CD4CD25T cells, compromising the effectiveness of immune prophylaxis and potentially leading to immune failure. However, the role of chicken CD4CD25T cells in chicken coccidia infection is not well understood. This study aimed to elucidate the immunomodulatory function of CD4CD25T cells during Eimeria maxima infection and assess the impact of CD25cell depletion on immune response and infection outcomes. The study comprised three trials: (1) examining CD4CD25T cells and cytokine changes post-E. maxima infection, (2) assessing the impact of in vitro CD25cell depletion on the immunomodulatory function of peripheral blood mononuclear cells (PBMCs) and (3) evaluating the effects of in vivo CD25cell depletion on PBMC function and E. maxima infection. The results revealed that E. maxima infection significantly increased CD4CD25T cell proportions in PBMCs and spleen, along with upregulated mRNA levels of IL-10, TGF-β and IL-4. In vitro CD25cell depletion enhanced PBMC proliferation as well as Th1, Th2 and Th17 response. In vivo CD25cell depletion partially disrupted E. maxima infection, as evidenced by reduced weight loss, alleviated intestinal lesions, lower oocyst shedding, and an anticoccidial index (ACI) exceeding 120. In conclusion, E. maxima infection upregulates CD4CD25T cells along with their associated cytokines (IL-10 and TGF-β) and the surface molecule CTLA-4; and the depletion of CD25cells restores protective Th responses (Th1, Th2 and Th17), while blockade of CD25 in vivo mitigates the E. maxima infection process. This study demonstrates the immunomodulatory role of CD4CD25T cells during E. maxima infection, providing key insights for elucidating the immune evasion mechanisms of this parasite.