Effect Of Flagellin On Immune Activation In HIV-1 Infection

Objective:HIV-1 infection caused intestinal barrier damage and obstacles,leading to part of the intestinal microbial translocation into the blood circulation.Intestinal microbial translocation to stimulate the body,induced immune response,and then cause the immune system is activated.Because chronic immune activation is one of the main characteristic of HIV-1 infection,it is also an important cause of the deterioration of HIV/SIV.The bacterial flagella as an important organ of bacterial movement,in the case of intestinal environment was destroyed,is easily divorced from the bacteria,in a free state.Flagellin constitutes the flagellum terminal filaments,and has a strong immunogenicity.Whether flagellin has effect in HIV-1 infection,whether it has an activation immune response,we need to further explore.Methods:Randomly collected 26 cases of normal healthy people and 98 cases of AIDS blood samples,patients with AIDS were randomly divided into HIV-infected group(CD4<200,n=52)and AIDS(CD4>200,n=46)group according to the number of CD4+ T cells in the plasma.The levels of iFABP and flagellin in plasma were measured by ELISA and the viral load of HIV-1 was detected by real-time quantitative RT-PCR.For further experiments in vivo,human peripheral blood mononuclear cells derived from macrophages cultured in vitro were treated with recombinant purified flagellin and infected with HIV-1 Bal strain virus.The expression of viral infection and inflammatory cytokines in macrophages was detected by real-time quantitative RT-PCR,ELISA and western blot.Results:The viral load of HIV-infection group and AIDS group was 4.269±0.1078copies/ml(log 10,n=52)and 4.617±0.1006copies/ml(log 10,n=46)respectively.The plasma virus of AIDS group was higher than HIV-infection group(P<0.5).IFABP and flagellin were detected in healthy and AIDS patients,but the levels of iFABP and flagellin in plasma of AIDS patients were significantly higher than those of healthy human plasma iFABP and flagellin.With the progress of AIDS,plasma CD4+T cells decreased,while the plasma iFABP content increased.The plasma CD4+ T cells and viral load were positively correlated with flagellin(r=0.1825,P=0.0751;r=0.2108,P=0.0382),but not with iFABP.Flagellin inhibits the replication of HIV-1 on macrophages at both gene level and protein level,and the inhibitory effect has a time and dose depend effect.Proinflammatory cytokine,like TNF-a and interleukin(IL-1?,IL-6 and IL-8)were significantly up-regulated in human macrophages pretreated with flagellin.The expression of cytokines(IFN-?),which are anti-HIV-1,was significantly up-regulated,but other antiviral factors such as IFN-?,APOBEC3A and APOBEC3G were irregular.Conclusion:HIV-1 infection causes intestinal barrier damage and promotes bacterial translocation,and as the viral load increases,the amount of bacterial translocation to the circulatory system increases.The flagellin,which is the main component of bacteria,can induce the high expression of proinflammatory cytokines,and further promote the degree of immune activation.Intestinal microbial translocation induced immune activation,will lead to accelerated progression of HIV-1 course.