responses of human endothelial cells to pathogenic and non-pathogenic leptospira species反应人类内皮细胞的致病性和非致病性钩端螺旋体的物种.pdfVIP

Responses of Human Endothelial Cells to Pathogenic and Non-Pathogenic Leptospira Species 1,2 2 2 Denise G. Martinez-Lopez , Mark Fahey , Jenifer Coburn * 1Tufts University School of Medicine, Boston, Massachusetts, United States of America, 2 Division of Infectious Diseases, Center for Infectious Disease Research, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America Abstract Leptospirosis is a widespread zoonotic infection that primarily affects residents of tropical regions, but causes infections in animals and humans in temperate regions as well. The agents of leptospirosis comprise several members of the genus Leptospira, which also includes non-pathogenic, saprophytic species. Leptospirosis can vary in severity from a mild, non- specific illness to severe disease that includes multi-organ failure and widespread endothelial damage and hemorrhage. To begin to investigate how pathogenic leptospires affect endothelial cells, we compared the responses of two endothelial cell lines to infection by pathogenic versus non-pathogenic leptospires. Microarray analyses suggested that pathogenic L. interrogans and non-pathogenic L. biflexa triggered changes in expression of genes whose products are involved in cellular architecture and interactions with the matrix, but that the changes were in opposite directions, with infection by L. biflexa primarily predicted to increase or maintain cell layer integrity, while L. interrogans lead primarily to changes predicted to disrupt cell layer integrity. Neither bacterial strain caused necrosis or apoptosis of the cells even after prolonged incubation. The pathogenic L. interrogans, however, did result in significant disruption of endothelial cell layers as assess