Metabonomic Studies Of BALB/c Mice Coinfected By Salmonella Typhimurium And Schistosoma Iaponicum

Coinfection refers to the phenomenon in which one host is infected by two or more pathogens. Of widespread in the world, it is estimated that one sixth of the world population affected by coinfection. Besides, parasite-related coinfection reached 800 million people. Coinfection primarily influences the infectious ability of pathogens, hosts’susceptibility, hosts’ clinical symptoms, and prevention of these infectious diseases and so on. Although coinfection is a big threat to human health, current researchs on it are relatively fewer, and more of them focused on several most important pathogens, such as HIV, HBV, HCV and some parasites which are endemic in Africa and Latin America. In the coinfection researches, more are epidemiological studies, and research on interaction between different pathogens are less. Therefore, this paper chooses Salmonella Typhimurium and Schistosoma japonicum coinfection in BALB/c mice to study interactions between the two pathogens and the effects on mice.Before coinfection research, we infected BALB/c mice with Salmonella Typhimurium mimicking the process of natural infection to create an animal model with salmonellosis. Then we tested and analyzed the influence of infection on metabolism of hosts urine, serum, liver, spleen and intestine, using metabonomic method based on NMR technology. Experimental results show that, sub-lethal dose of Salmonella Typhimurium can colonize intestinal tract of mice and developed into salmonellosis. Infection greatly influenced structure and metabolism of ileum and spleen, the effect on liver and serum is not very big. Dynamic changes of urine metabolism in infected mice reflect the development process of salmonellosis. In addition, Salmonella Typhimurium infection restrained the utilization of hosts’energy source, disrupted hosts’material metabolism and intestinal microecological balance. The results also showed responses of host to Salmonella Typhimurium infection. These responses include " colonization resistance" of intestinal micro flora, immune polarization of host immune system and production of itaconic acid. Based on the first part of the paper about Salmonella Typhimurium infection and the former studies on Schistosoma japonicum infection in BALB/c mice, we infected BALB/c mice with Schistosomiasis japonica and Salmonella Typhimurium successively to create animal model for coinfection in order to reveal the effect of Salmonella Typhimurium infection on Schistosomiasis development. Experimental results show that, infection of Salmonella Typhimurium five weeks after Schistosoma japonicum infection can reduce adult Schistosoma japonicum, reduce the number of Schistosoma japonicum eggs in liver, and decrease the severity of Schistosomiasis. All these directly led to increased survival rate of of mice coinfected. In addition, by comparing the metabolic changes of liver and serum in infected and coinfected mice, we found that Salmonella Typhimurium played a role in the coinfected animal group, reducing the impact of Schistosomiasis on mice. Dynamic changes of urine metabolite in different animal groups also demonstrated the impact of Salmonella Typhimurium infection on Schistosomiasis in mice. We also tested serum level of IL-4 and IFN-y in different animal groups and found that Salmonella Typhimurium infection reduced the content of IL-4 in serum of mice with shistosomiasis, increased the content of IFN-y. This indicates that Salmonella Typhimurium infection affected schistosomiasis development, mainly depending on its ability to turn Th2 immune polarization to Thl immune polarization. In progress of immune polarization turning, adult schistosomes were killed and these reduced the total number of schistosome eggs in experimental mice, thus reduced the destruction of Schistosoma japonicum infection.In my thesis, the study was divided into two parts. The first part is about the influence of Salmonella Typhimurium infection on hosts’ metabolism and we also discussed the occurrence and development of salmonellosis in experimental mice as well as hosts’response to pathogenic bacteria infection. The second part is about Salmonella Typhimurium and Schistosoma japonicum coinfection in which one pathogen became inhibitor of another pathogenic organism. All these results are helpful for people to deepen the understanding of associated pathogenic infections, so as to prevent this kind of infection and develop better ways to treat these infectious diseases.