The Molecular Mechanism Of ?2 Integrin Facilitates Salmonella Invasion Into Host Cells

Salmonellosis is an important zoonotic disease in public health.The disease is caused by Salmonella,which is an important food-borne pathogen and poses a great threat to human health and food safety.The microbe-host interactions are critical steps in the pathogenesis of bacterial infection.During the infection process,Salmonella is able to invade the host cells successfully and inhibit the multiple mechanisms of sterilization by interacting with the host factors,using or hijacking the host signaling pathways,so as to achieve its survival within the cells,thus completing the entire infection process.Bacterial invasion of host cells is the first,and also the most important step in establishing infection process.Recently,some host factors required for Salmonella infection have been characterized.In order to find novel host factors for Salmonella invasion and to gain deeper insight into Salmonella pathogenicity,we employed an overexpression assay combined with Salmonella infection strategy to screen potential host factors for Salmonella infection.The results showed that ?2 integrin(ITGB2)could facilitate Salmonella invasion of host cells.We found that Salmonella infection rate was significantly higher in HeLa cells overexpression with ?2 integrin,whereas silencing the expression of ?2 integrin significantly markedly inhibited Salmonella infection of cells.These results suggesting that ?2 integrin is a key host factor for Salmonella infection.Bacterial pulldown assay revealed that ?2 integrin interacted with Salmonella specifically.A strong colocalization of ?2 integrin and Salmonella on the surface of cells was obserbed by laser-scanning confocal microscope.We further found that ?2 integrin and Salmonella are internalized together into cells by flow cytometry and cellular immunofluorescence analysis.In addition,Antibodies to ?2 integrin significantly blocked Salmonella infection in cells.?2 integrin ectodomain soluble protein inhibited the infectivity of Salmonella infection in cells.These results further indicates that ?2 integrin plays an important role in early invasion of Salmonella infection.Moreover,the truncated forms of ?2 integrin extracellular region were expressed and functionally verificated,we further confirmed that the role of ?2 integrin facilitated Salmonella invasion depends on its I-like domain.Together,this study reveals the molecular mechanism of ?2 integrin facilitating Salmonella invasion into host cells.These findings not only help to study and understand the pathogenic mechanism of Salmonella,but also provide important scientific basis for the prevention and treatment of Salmonella infection.