circulating lipoproteins are a crucial component of host defense against invasive salmonella typhimurium infection循环脂蛋白是宿主防御入侵的关键组件鼠伤寒沙门氏菌感染.pdfVIP

Circulating Lipoproteins Are a Crucial Component of Host Defense against Invasive Salmonella typhimurium Infection 1,2 1,2 1,2 3 1 Mihai G. Netea , Leo A. B. Joosten , Monique Keuter , Frank Wagener , Anton F. H. Stalenhoef , Jos W. M. van der Meer1,2, Bart Jan Kullberg1,2* 1 Division of General Internal Medicine, Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands, 2 Nijmegen Institute of Infection, Inflammation and Immunity (N4i), Nijmegen, The Netherlands, 3 Department of Pharmacology and Toxicology, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands Abstract Background: Circulating lipoproteins improve the outcome of severe Gram-negative infections through neutralizing lipopolysaccharides (LPS), thus inhibiting the release of proinflammatory cytokines. Methods/Principal Findings: Low density lipoprotein receptor deficient (LDLR2/ 2) mice, with a 7-fold increase in LDL, are resistant against infection with Salmonella typhimurium (survival 100% vs 5%, p ,0.001), and 100 to 1000-fold lower bacterial burden in the organs, compared with LDLR+/+ mice. Protection was not due to differences in cytokine production, phagocytosis, and killing of Salmonella organisms. The differences were caused by the excess of lipoproteins, as hyperlipoproteinemic ApoE2/ 2 mice were also highly resistant to Salmonella infection. Lipoproteins protect against infection by interfering with the binding of Salmonella to host cells, and preventing organ invasion. This leads to an al