Protective vascular coagulation in response to bacterial infection of the kidney is regulated by bacterial lipid A and host CD147

• Published in: Pathogens and disease 2018-11, Vol.76 (8)
• Main Authors: Schulz, Anette, Chuquimia, Olga D, Antypas, Haris, Steiner, Svava E, Sandoval, Ruben M, Tanner, George A, Molitoris, Bruce A, Richter-Dahlfors, Agneta, Melican, Keira
• Format: Article
• Language: English
• Subjects: Acylation; Animals; Bacteria; Bacterial diseases; Bacterial infections; Bacterial Infections - blood; Bacterial Infections - immunology; Bacterial Infections - metabolism; Basigin - metabolism; Biomarkers; Blood Coagulation; Capillaries; CD147 antigen; Cell Line; Clear cell-type renal cell carcinoma; Coagulation; Cytokines - metabolism; Disease Models, Animal; E coli; Endothelial cells; Epithelial cells; Epithelial Cells - metabolism; Epithelial Cells - microbiology; Humans; In vivo methods and tests; Infections; Inflammation Mediators - metabolism; Kidneys; Lipid A; Lipid A - immunology; Lipids; Lipopolysaccharides; Male; Medicin och hälsovetenskap; Nephritis - etiology; Nephritis - metabolism; Proteome; Proteomics - methods; Rats; Sepsis; Signal Transduction; Tissue factor; Toxins
• ISSN: 2049-632X; 2049-632X
• DOI: 10.1093/femspd/fty087

Abstract Bacterial infection of the kidney leads to a rapid cascade of host protective responses, many of which are still poorly understood. We have previously shown that following kidney infection with uropathogenic Escherichia coli (UPEC), vascular coagulation is quickly initiated in local perivascular capillaries that protects the host from progressing from a local infection to systemic sepsis. The signaling mechanisms behind this response have not however been described. In this study, we use a number of in vitro and in vivo techniques, including intravital microscopy, to identify two previously unrecognized components influencing this protective coagulation response. The acylation state of the Lipid A of UPEC lipopolysaccharide (LPS) is shown to alter the kinetics of local coagulation onset in vivo. We also identify epithelial CD147 as a potential host factor influencing infection-mediated coagulation. CD147 is expressed by renal proximal epithelial cells infected with UPEC, contingent to bacterial expression of the α-hemolysin toxin. The epithelial CD147 subsequently can activate tissue factor on endothelial cells, a primary step in the coagulation cascade. This study emphasizes the rapid, multifaceted response of the kidney tissue to bacterial infection and the interplay between host and pathogen during the early hours of renal infection. Kidney response to infection is influenced by both host and pathogen. The structure of bacterial LPS effects the kinetics of protective coagulation, while infected epithelia releases CD147, activating tissue factor.