Establishment Of BALB/c Mice Model For The Chronic Melioidosis Caused By Burkholderia Pseudomallei

ObjectiveBurkholderiapseudomallei existsin the soil or water in the epidemic areas.Burkholderia pseudomallei infects both animals and human beings and causes melioidosis.More and more evidence confirmed that the melioidosis is a spreading zoonosis.The host's immune response plays an important role in the pathogenesis of melioidosi;however,its infection mechanism is unclear,and animal model research needs to be further developed.Burkholderiapseudomalleiinfection usually causes acute or chronic melioidosis in host,but chronic melioidosis is more prevalent in population and shows persistentpathological changes inviscera.Therefore,in this study we established a chronically infecting mice model to mimic melioidosis.After the infection,we measured bacterial colonization and serum inflammatory factors to assess the stability of this model.The study fills the gaps in the domestic chronic melioidosis disease modeland lays a solid foundation for the study of pathogenic mechanism of melioidosis,and for the development of vaccine,evaluation of drug in the future.Methods1.BALB/c mice were intranasallychallenged with different doses of B.pseudomallei.Then mice were monitored daily for 42 days.The survival rate was recorded.2.On day21,day28,day35 and day42 post infection,the bacterial colonized in blood and organs were determined by Q-PCR and culturing in vitro.3.The pathological changes of organs were assessed byHE staining.4.Cytokines(TNF-? and IFN-?)and specific IgG antibodies were detected by ELISA.Results1.After challenging by a low dosage B.pseudomallei,60% of mice survived on day42.2.After challenging,the mice continually lost weights until sacrificed.3.Typical pathological changes presented inorgans of the infected mice.The highest colonization was observed in the spleens.Blood,livers,and lungs were also significantly colonized by the bacteria.4.The titer of the serum specific IgG antibodies increased continuously until 21 days.post challenge.The expression levels of TNF-? and IFN-? were much higher in experimental group compared with those in controls.ConclusionThese results suggested that we successfully established chronic B.pseudomallei infecting BABL/c mouse model,and provided a useful model for the development and evaluation of vaccine and therapeutics for controlling B.pseudomalle infection.