Abstract Cytokine storm has serious harmfulness in infectious diseases, but its regulatory mechanism is not clear. The immunopathology is mediated by local overproduction of Th1-type cytokines during acute infection with Toxoplasma gondii (T. gondii). Because dendritic cells (DCs) are essential in the elicitation of these immune responses, we investigated the presence the role of plasmacytoid dendritic cells (pDCs) upon T. gondii infection. Towards this goal, we examined T. gondii infection of BDCA2-DTR mice, which specifically depleting this cell population. Here, we found that T. gondii infection reduced the number of pDCs, and depletion of pDCs in BDCA2-DTR mice were extremely susceptible to T. gondii infection, with decreased serum levels of IL-12, but increased serum levels of IFN-γ, IL-6 and TNF-α. In addition, depletion of pDCs also increased IFN-γ production by CD4+T cells, and resulted in an exacerbation of immunopathological damage caused by T. gondii infection. These results reveal that pDCs play a protective role during T. gondii infection by modulation of cytokine triggers immune response.