The role of regulatory T cells during Plasmodium chabaudi chabaudi AS infection in BALB/c mice

An inappropriate immune response to parasite infection is one of the primary drivers of malaria pathogenesis. Regulatory T cells (Tregs), an important subset of CD4+ T cells, can maintain self‐tolerance and prevent autoimmune diseases. However, there is little consensus about their role in malaria pathogenesis. In this study, we transiently depleted Tregs (CD25+ T cells) using an anti‐CD25 mAb (7D4 clone) at different time points following Plasmodium chabaudi chabaudi AS infection in BALB/c mice and investigated the effect of depletion of Tregs in this model. In control mice, Tregs proliferated significantly and their suppressive function was enhanced after infection. IL‐10 was increased drastically during infection. Depletion of Tregs at various time points can lead to divergent outcomes. When Tregs were depleted prior to or during the early phase of infection, most mice survived and had a robust Th1 immune response. In contrast, when Tregs were depleted close to peak parasitemia, all mice died as a result of inflammation. Taken together, these data suggest that in P. c. chabaudi AS‐infected BALB/c mice, Tregs inhibit the Th1 response and macrophage activation, leading to increased parasite load; however, they also control inflammation‐mediated pathology by secreting high levels of IL‐10.

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