The Research On The Toxicity Of L. Pneumophila And The Mechanisms That Causes Varying Reactions On The Host's Immune System

Legionella pneumophila(L.pneumophila)is a pathogen that ubiquitously exits within the natural aquatic environments.Almost 90%infections are caused by L.pneumophila serogroup I.L.pneumophila infects humans to cause Legionnaires'disease(LD)as well as a milder form known as Pontiac fever.Although L.pneumophila is a widespread disease worldwide,no satisfactory method of detecting L.pneumophila virulence has been reported so far.In present study,we demonstrated that different strains of L.pneumophila could induce different levels of activation to NF-?B signaling pathway in vitro.We also found that the virulence of each L.pneumophila strain was positively correlated with its ability to activate NF-?B signaling pathway.By using mouse model which is susceptible to L.pneumophila infection,we found that L.pneumophila strains which could induce higher NF-?B activation in vitro showed more obvious weight losses and higher mortality.HE staining showed more severe lung inflammation in the strain inducing higher NF-?B activation.And those strains with abilities to induce higher NF-?B activation in vitro also have higher serum cytokine concentrations.Therefore,our study presented a positive correlation between the virulence in mouse model of L.pneumophila strains and their abilities to activate NF-?B signaling pathway in vitro.We compared the immune response of host immune system against different strains,the results showing that L.pneumophila strains cause different host immune reactions.Strains which induce higher activation of NF-?B signaling pathway cause strong immune responses.Strains with higher abilities to activate NF-?B signaling pathway also have higher abilities to activate the immune cells in vivo.In vivo,highly activated NK cells exhibit a depleted phenotype,probably due to the activation induced apoptosis.We also demonstrated through experiment that the difference in activation of NF-?B signaling pathway occurs at the level of TAB1 and TAB2 adaptor proteins.We also try to find out the reasons for this difference by gene level analysis.Our results reveal a new potential method of evaluating the virulence of L.pneumophilain vitro and will have a positive impact on the prevention and control of L.pneumophila.