| Toxoplasma gondii(T.gondii)is an obligate intracellular parasite that affects almost all warm-blooded animals.T.gondii exists in three major forms: tachyzoites,bradyzoites and oocysts.Human-beings acquire infection by ingesting bradyzooites in undercooked meat or by ingesting oocysts shed in cat feces.Currently,more than a third of the world’s population is at risk of being infected by T.gondii.It is usually appears as inapparent infectious after infected with T.gondii.However,for immunocompromised hosts,Toxoplasma encephalitis may be triggered by central nervous system infection,which in turn causes a series of brain lesions and systemic disseminated infections,usually manifested as a single or multiple brain abscesses,and it can also cause a diffuse ventriculitis or encephalitis.In recent years,as a ubiquitous zoonotic parasitic disease,T.gondii also presents a degree of threat to human health.Therefore,the mechanism of interaction between T.gondii and host cells has become one of the research hotspot.Human Toxoplasma encephalopathy is mainly caused by T.gondii type II strains.And ME49 strain T.gondii is a typical Type II strain.It is a weakly virulent strain that prefers to infect CNS and can traverse the blood-brain barrier(BBB)to cause damage to various neural cells in the host’s brain,which will affects the host’s ability to identify,learn,and memory.Brain microvascular endothelial cells are the main component of BBB,and T.gondii replicates and lyses in endothelial cells before the invasion of CNS.At present,a large amount of research has been conducted on the pathogenicity of T.gondii,however,the interaction mechanism between T.gondii and the host’s blood-brain barrier is limited currently.The proteomics study of mouse brain tissue was carried out by i TRAQ(isobaric Tags for Relative and Absolute Quantification)combined with LC-MS/MS(Liquid chromatography-tandem mass spectrometry).Interestingly,we found that the expression of complement 3(C3)increased 11-fold after infection with T.gondii.According to reports,T.gondii-associated Complement C3 a is not only an anaphylatoxin,which promotes inflammatory response,but also it affects many tissues of the body and their blood-tissue barriers.After the T.gondii invades the host’s central nervous system,it enters the stage of chronic infection.Due to the work of the body’s immune system,it is difficult to form new cysts at this stage.Because of the blockage of the blood-brain barrier,there is currently little drug to clear the cysts.The replication of T.gondii in the brain microvascular endothelial cells may be the last chance for tachyzoites to proliferate! Does the C3 a molecule affect the replication and proliferation of T.gondii in brain microvascular endothelial cells by affecting the mitochondrial function of microvascular endothelial cells?By artificially increasing the content of C3 a in mice’s systemic blood flow after infection,we found that when the systemic C3 a content increases,the number and volume of brain cysts formed in the mouse brain increased.How does the C3 a molecule affect BBB,causing increased brain cysts? We used immunofluorescence,flow cytometry,and other research methods to study the effect of C3 a molecules on mouse brain microvascular endothelial cells(b End3)in vitro.We found that under the influence of low-dose C3 a molecules,the mitochondria in b End3 cell were severely damaged,and there is less replication of tachyzoites in the vacuoles.And under the influence of high-dose C3 a molecules,mitochondrial damage of endothelial cells is lighter,and tachyzoites in the vacuoles increase.These findings suggest that mitochondria of host brain microvascular endothelial cells may play an important role in the infection and pathogenesis of toxoplasmosis.It will not only add new theoretical basis for the invasion of the host barrier system by T.gondii,but also provides new ideas for the prevention,diagnosis and drug development of T.gondii. |
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