Research About Listr1 Locus Influence The Susceptibility Of Plasmodium Yoelii In Mice

Objective :In recent years,the importance of liver as an immune organ has been paid more and more attention.Many researches have shown that liver plays a key role in the innate immune when defensing against systemic infection.Malaria is a serious infectious disease threatening human health,and it is also a typical systemic infectious disease.At present,the role of liver immunity in anti-malaria immunity,especially in blood stage,is not clear.Previously,we have found that Listr1 locus can control the innate immunity against Listeria infection in mouse liver.Based on the similarity between Listeria infection and blood stage malaria,we suggest that Listr1 locus may also influence the susceptibility of mice to malaria.In this study,we established a mouse malaria model infected with Plasmodium yoelii by using the congenic mice of Listr1 locus.We investigated the effects of Listr1 locus on the process and outcome of malaria infection,the load of parasites and the production of inflammatory cytokines in liver and spleen tissues at different time points after infection;the immune cell subsets and functions in liver and spleen tissues,and the pathological changes in liver of mice.In order to prove that Listr1 locus can regulate the susceptibility of mice to malaria and reveal its immunological mechanism.We also want to provide a new way to control malaria infection,and experimental basis for elucidating the mechanism of Listr1 locus.Methods: C.B6By-Listr1 mice(bearing the C57BL/6-derived Listr1 locus on a BALB/c background)and BALB/c mice were infected with P.y17 XL to observe the difference of survival rate and infection rate.We observed the liver pathological damage after five days of P.y17 XL infection in the two mice by HE stain;And quantitative PCR was used to detect the level of parasite load in liver and spleen tissues after P.y17 XL infection at different time points.Quantitative PCR was also used to detect the level of IL-1??IL-6?IL-8?i NOS?TNF-??IL-10?IFN-??MCP-1 in liver and spleen tissues after 24 h and 48 h infected with P.y17 XL.And flow cytometry was used to detect the phenotypes and percentage of IFN-? secreting cells in spleen of the two mice,and detect the phenotypic differences of liver mononuclear cells in Rag2-/-C.B6By-Listr 1 and Rag2-/-BALB/c mice.Results: The infection rates of C.B6By-Listr1 mice were significant higher than BALB/c mice at day4 to day8 post the infection(p<0.05).C.B6By-Listr1 mice died at day 7 to day 9 post the infection.Half of the BALB/c mice died at day 8 to day 9 post the infection.The rest mice survived until 13 days after infection.And there was a significance difference in survival rate between them(p<0.01).On the first day and the second day after P.y17 XL infection,the difference of parasite load level was observed in the liver tissues of the two mice.On the third and fifth day after P.y17 XL infection,the difference of parasite load level was found in the spleen tissues of the two mice.And the parasite load of C.B6ByListr1 mice were higher than that of the BALB/c mice in spleen and liver(P < 0.05).The HE staining show that there were more malarial pigment deposition in C.B6By-Listr1 liver;but the malarial pigment were nearly not seen in BALB/c mice five days after P.y17 XL infection.The levels of IL-6(P<0.05),TNF-a(P<0.05)and MCP-1(P<0.01)in liver tissues of BALB/c mice 48 hours after P.y17 XL infection were significantly higher than those of C.B6By-Listr1 mice.The level of IFN-?(P<0.05)in spleen tissue of BALB/c mice 24 and 48 hours after P.y17 XL infection was significantly higher than that of C.B6By-Listr1 mice.In spleen,CD3+T cells but not CD49+ NK cells secret IFN-?,and the percentage of CD3+ IFN-?+ cells in BALB/c mice was higher than that in C.B6By-Listr1 mice.In liver,the expression of CX3CR1 and CCR2 in Rag2-/-BALB/c mice CD14+cells was higher than that in Rag2-/-C.B6By-Listr1 mice.Conclusions : 1 Listr1 locus can control the susceptibility of mice to malaria.2 Listr1 locus can affects the release of inflammatory cytokines and the clearance of erythrocyte in the early stage of malaria infection in mice liver and spleen.3 CD3 + T cells in spleen participate in Listr1 locus regulation process,and CD14 + monocytes / macrophages in liver may participate in this regulation process.