Plasmacytoid Dendritic Cells Influence To Immune Response During Acute Inflammation With Toxoplasma Gondii Infection

Toxoplasma gondii(T.gondii)is an obligate intracellular parasite,infection with T.gondii usually cause asymptomatic,it become deadly opportunistic protozoa in congenital and immunocompromised individuals.Early in infection,one of the first innate cells to respond is Dendritic cells(DCs).As one of the most important antigen-presenting cell in immune system,DCs can activate T cells to initiate adaptive immune response,is a bridge between innate and adaptive immunity.DCs are a heterogeneous group,including a variety of subsets.The biological effect of DCs due to cell type and quantity,therefore,the study of DCs subsets responding to T.gondii infection is becoming a hot spot.DCs can be divided into Classical Dendritic cells(cDCs)and Plcasmacytiod Dendritic Cells(pDCs).pDCs are special subset of DCs,which can selective induce immune response or immune tolerance in difference microenvironments.Recent study has shown that pDCs can recognize and prssentation of parasite-derived antigen to T cells in T.gondii infection.When pDCs were depleted,significantly increase in the sensitivity of TLR11-/-mice to T.gondii challenge.However,the mechanism of pDCs regulating innate and adaptive immune cells during acute infection with T.gondii is not clearly.Using modern immunology experimental technique combined with pDCs gene conditional knockout mice to study and in-depth understanding the regulatory mechanisms of pDC in innate and adaptive immune cells during acute infection with T.gondii.This study will better understanding of the role of pDCs in the infection immunity and contribute to study effective Dendritic Cell vaccine in T.gondii infection provide new targets.This study is mainly carried out by the following aspects and the following results:1.pDCs ablation increases the susceptibility of mice to T.gondiiIn this study,DT were injected intraperitoneally administration specifically depletes pDCs in BDCA2-DTR mice,then infected i.p with T.gondii tachyzoites 3 days.There revealed a markedly increased susceptibility of BDCA2-DTR mice relative to wild-type mice,the mortality rate increase 45%.These results suggest that pDCs plays a important role in anti-T.gondii infection.2.pDCs ablation leads to a decrease in IL-12 secretionDetection of IL-12 secreted by serum in infected mice showed a significant decrease in IL-12p40 secretion in pDCs deleting mice compared with the control group,and IL-12p70 was not detected.The result suggest that pDCs plays a regulatory role in the synthesis and secretion of IL-12.3.pDCs ablation increased the secretion of Th1-type cytokines during acute infection with T.gondiiDetection of secreted levels of Th1 cytokines secreted by serum amounts from infected mice revealed a significant increase in high-secreted IFN-?,IL-6 and TNF-? after pDCs deletion.The results suggest that pDCs deficiency aggravation Th1 type cytokine storms.4.pDCs ablation impacts the number of macrophages and cDCsDetection of the effect of infected spleen cells found that pDCs deletion did not affect the number of neutrophils and inflammatory monocytes in innate immune cells.But pDCs deletion caused significant reduction in the number of macrophages and cDCs.Further analysis of the subset of cDCs: CD8+DCs and CD11b+DCs,found that pDCs deletion mainly resulted in a significant reduction in the proportion and number of CD8+DCs.In order to detect whether pDCs deletion can effects CD4+T cells and CD8+T cells,The data revealed that T.gondii infection resulted in a significant reduction in T cells,but pDCs deletion did not affect the number of T cells.These results suggest that pDCs and macrophages or CD8+DCs exist in cross-talk.5.pDCs ablation causes CD4+T cells hyperpolarizingAfter 3 days infection by T.gondii,IFN-? was mainly secreted by CD4+T cells,and pDCs deletion did not affect IFN-? secreted by NK cells.pDCs deletion significantly increased the frequency and number of IFN-?-positive CD4+T cells,the frequency IFN-?-positive CD8+T cells increased,but the number of these cells significantly decreased.Theses results suggest that deletion of pDCs leads to CD4+T cells hyperactivation.In conclusion,pDCs affects the secretion of IL-12 and plays a protective role in the early T gondii infection,affecting the number of macrophages and CD8+DCs in innate immune cells.pDCs also impact the ability of CD4+T to secrete IFN-? in adaptive immune cells and regulate secretion of Th1-type cytokines.