Divergence of Protection Induced by Bacterial Products and Sepsis-Induced Immune Suppression

• Published in: Infection and Immunity Vol. 73; no. 8; pp. 4905 - 4912
• Main Authors: Sterns, Theo, Pollak, Nils, Echtenacher, Bernd, Männel, Daniela N
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01-08-2005
• Subjects: animal models; Animals; bacteria; Bacterial diseases; Bacterial sepsis; Bacteriology; Biological and medical sciences; Cytokines - metabolism; Fundamental and applied biological sciences. Psychology; Host Response and Inflammation; Human bacterial diseases; Immune Tolerance - drug effects; Immune Tolerance - immunology; Infectious diseases; innate immunity; interleukin-10; interleukin-6; lipopolysaccharides; Lipopolysaccharides - immunology; Medical sciences; Mice; Mice, Inbred C57BL; Microbiology; Miscellaneous; peritonitis; Salmonella enterica subsp. enterica serovar Typhimurium; Salmonella Infections, Animal - immunology; Salmonella Infections, Animal - mortality; Salmonella typhimurium - immunology; salmonellosis; Sepsis - immunology; serotypes; Time Factors; Tumor Necrosis Factor-alpha - pharmacology; tumor necrosis factors; Infection; Sepsis syndrome; Microbiology; Suppression; Bacteriosis; Bacteria; Immunity; Bacteremia
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.73.8.4905-4912.2005

Susceptibility to bacterial infections after a primary immune stimulation differs drastically depending on the presensitization of the innate immune system. To determine the conditions that either induce protection or enhanced susceptibility to infection with Salmonella enterica serovar Typhimurium, we pretreated mice either with tumor necrosis factor (TNF), whole killed bacteria, or sublethal cecal ligation and puncture (CLP) as a mouse model for septic peritonitis. Impaired production of the cytokines TNF, interleukin-6 (IL-6), and IL-10 was induced by these pretreatment schedules, with TNF-signaling not being essential for this effect. Injection of TNF or killed bacteria enhanced survival of mice infected subsequently with serovar Typhimurium. In contrast, sepsis such as that induced by CLP only protected from shock induced by D-galactosamine and lipopolysaccharide or by a high dose of bacteria but sensitized to a secondary bacterial infection. Such sepsis-induced enhanced susceptibility to infection was critically dependent on TNF function.