title: Enhanced Expression of T-Cell Immunoglobulin and Mucin Domain Protein 3 in Endothelial Cells Facilitates Intracellular Killing of Rickettsia heilongjiangensis.
abstract: Rickettsia heilongjiangensis is the pathogen of Far eastern spotted fever, and T-cell immunoglobulin and mucin domain protein 3 (Tim-3) is expressed in human vascular endothelial cells, the major target cells of rickettsiae. In the present study, we investigated the effects of altered Tim-3 expression in vivo in mice and in vitro in human endothelial cells, on day 3 after R. heilongjiangensis infection. Compared with corresponding controls, rickettsial burdens both in vivo and in vitro were significantly higher with blocked Tim-3 signaling or silenced Tim-3 and significantly lower with overexpressed Tim-3. Additionally, the expression of inducible nitric oxide synthase and interferon γ in endothelial cells with blocked Tim-3 signaling or silenced Tim-3 was significantly lower, while the expression of inducible nitric oxide synthase, interferon γ, and tumor necrosis factor α in transgenic mice with Tim-3 overexpression was significantly higher. These results reveal that enhanced Tim-3 expression facilitates intracellular rickettsial killing in a nitric oxide-dependent manner in endothelial cells during the early phase of rickettsial infection.
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology.
authors.forename: Jun
authors.initials: J
authors.lastname: Jiao
authors.affiliation: Department of Molecular Immunology, Beijing Institute of Basic Medical Sciences.
authors.forename: Gencheng
authors.initials: G
authors.lastname: Han
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology.
authors.forename: Wenping
authors.initials: W
authors.lastname: Gong
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology Department of Clinical Laboratory, 105th Hospital of the People's Liberation Army, Anhui, China.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Xiong
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology.
authors.forename: Bohai
authors.initials: B
authors.lastname: Wen
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D000072597:Hepatitis A Virus Cellular Receptor 2; D054884:Host-Pathogen Interactions / Q000276:immunology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D012281:Rickettsia / Q000276:immunology*; D012282:Rickettsia Infections / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D014709:Vero Cells
chemical_list: C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins
keywords: Rickettsia heilongjiangensis; T-cell immunoglobulin and mucin domain protein 3; endothelial cells; spotted fever