OBJECTIVES: Alarmin high mobility group box 1 (HMGB1) is essential for correct DNA folding and transcription. It can be released from damaged cells or secreted by stimulated cells. HMGB1 has been detected in serum or plasma as a late marker of sepsis, but its suitability as a marker of sepsis has been disputed. METHODS: One-week-old germ-free piglets were orally infected/colonized with enteric bacterial pathogens (Salmonella Typhimurium or Escherichia coli O55) or with probiotic bacteria (E. coli Nissle 1917) for 24 h. The transcriptions of HMGB1, interleukin (IL)-8, tumor necrosis factor (TNF)-α, and IL-10 (quantitative reverse transcription and polymerase chain reaction), their protein levels (ELISA), and clinical state of the piglets (somnolence, anorexia, diarrhea, tachycardia, tachypnea, and tremor) were estimated. RESULTS: The piglets infected with enteric pathogens suffered from infections. HMGB1 was transcribed in the terminal ileum constitutively, regardless of any bacterial presence. In contrast, the transcription of cytokines was upregulated by virulent bacteria. HMGB1, IL-8, and TNF-α levels in the ileum were increased by both enteric pathogens, while IL-10 levels increased in E. coli O55-infected piglets only. HMGB1 significantly increased in the plasma of piglets infected with virulent E. coli only, but cytokine levels were in most cases increased by both virulent bacteria. HMGB1 and cytokine levels in ileum lavages and plasma of piglets colonized with probiotic E. coli remained comparable to those of the non-stimulated germ-free piglets. CONCLUSION: The local and systemic expression of HMGB1, its relationship to the inflammatory cytokines, and clinical findings showed HMGB1 as a suitable marker of severity of sepsis in the gnotobiotic piglet infection model.

• MeSH
• Bacterial Infections blood   immunology   microbiology   MeSH
• Biomarkers blood   MeSH
• Enzyme-Linked Immunosorbent Assay MeSH
• Escherichia coli growth & development   MeSH
• Germ-Free Life * MeSH
• Ileum metabolism   microbiology   MeSH
• Interleukin-10 blood   MeSH
• Interleukin-8 blood   MeSH
• Disease Models, Animal MeSH
• Animals, Newborn blood   immunology   microbiology   MeSH
• Reverse Transcriptase Polymerase Chain Reaction MeSH
• Swine MeSH
• HMGB1 Protein * blood   MeSH
• Diarrhea MeSH
• Salmonella typhimurium growth & development   MeSH
• Sepsis blood   immunology   microbiology   MeSH
• Severity of Illness Index MeSH
• Tachycardia MeSH
• Tumor Necrosis Factor-alpha blood   MeSH
• Tremor MeSH
• Inflammation blood   immunology   microbiology   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Biomarkers MeSH
• Interleukin-10 MeSH
• Interleukin-8 MeSH
• HMGB1 Protein * MeSH
• Tumor Necrosis Factor-alpha MeSH

The colonization, translocation and protective effect of two intestinal bacteria - PR4 (pig commensal strain of Bifidobacterium choerinum) or EcN (probiotic Escherichia coli strain Nissle 1917) - against subsequent infection with a virulent LT2 strain of Salmonella enterica serovar Typhimurium were studied in gnotobiotic pigs after oral association. The clinical state of experimental animals correlated with bacterial translocation and levels of inflammatory cytokines [a chemokine, interleukin (IL)-8, a proinflammatory cytokine, tumour necrosis factor (TNF)-α and an anti-inflammatory cytokine, IL-10] in plasma and intestinal lavages. Gnotobiotic pigs orally mono-associated with either PR4 or EcN thrived, and bacteria were not found in their blood. No significant inflammatory cytokine response was observed. Mono-association with Salmonella caused devastating septicaemia characterized by high levels of IL-10 and TNF-α in plasma and TNF-α in the intestine. Di-associated gnotobiotic pigs were given PR4 or EcN for 24 h. Subsequently, they were infected orally with Salmonella and euthanized 24 h later. Pigs associated with bifidobacteria before Salmonella infection suffered from severe systemic infection and mounted similar cytokine responses as pigs infected with Salmonella alone. In contrast, EcN interfered with translocation of Salmonella into mesenteric lymph nodes and systemic circulation. Pigs pre-associated with EcN thrived and their clinical condition correlated with the absence of IL-10 in their plasma and a decrease of TNF-α in plasma and ileum.

• MeSH
• Antibiosis * MeSH
• Bifidobacterium immunology   MeSH
• Cytokines analysis   blood   MeSH
• Escherichia coli immunology   MeSH
• Germ-Free Life MeSH
• Ileum immunology   microbiology   MeSH
• Colon immunology   microbiology   MeSH
• Swine MeSH
• Probiotics therapeutic use   MeSH
• Salmonella typhimurium immunology   MeSH
• Salmonella Infections, Animal immunology   therapy   MeSH
• Intestines immunology   microbiology   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Cytokines MeSH

Innate immunity is shaped by a complex of redundant and pleiotropic factors that ensure recognition, alert and suppression of pathogens. Innate immune responses in the gut are complicated by the requirement of parallel tolerance to commensal microflora predominating in cell numbers and species. In normal individuals, the intestinal mucosa together with relevant lymph nodes represents a robust barrier against systemic spread of non-typhoid Salmonella. Contemporary insights into these defense mechanisms are reviewed.

• MeSH
• Gastrointestinal Tract immunology   MeSH
• Humans MeSH
• Immunity, Innate * MeSH
• Salmonella immunology   MeSH
• Salmonella Infections immunology   MeSH
• Immunity, Mucosal * MeSH
• Intestinal Mucosa immunology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Reactive NO metabolites play a distinct role in the control of Salmonella enterica serovar Typhimurium (ST; a facultative intracellular pathogen) in susceptible host. A significant increase of nitrite and/or nitrate plasma levels, 3-nitro-tyrosine expression and pathological changes in mesenteric lymph nodes have been observed in gnotobiotic piglets orally infected for 1 d with a virulent strain of ST but not in piglets infected with a rough mutant of ST.

• MeSH
• Microscopy, Electron MeSH
• Phagocytosis MeSH
• Germ-Free Life MeSH
• Immunoenzyme Techniques MeSH
• Liver ultrastructure   MeSH
• Lymph Nodes metabolism   ultrastructure   MeSH
• Mesentery MeSH
• Swine, Miniature MeSH
• Nitric Oxide metabolism   MeSH
• Lung ultrastructure   MeSH
• Swine MeSH
• Salmonella typhimurium pathogenicity   MeSH
• Salmonella Infections, Animal immunology   metabolism   microbiology   pathology   MeSH
• Intestines ultrastructure   MeSH
• Tyrosine analogs & derivatives   metabolism   MeSH
• Virulence MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• 3-nitrotyrosine MeSH Browser
• Nitric Oxide MeSH
• Tyrosine MeSH

Before the onset of specific immune response, the host defence against Salmonella infection is regulated by cytokines characteristic for immunity to intracellular bacteria. Cytokine response to non-typhoidal Salmonellae is described.

• MeSH
• Cytokines biosynthesis   MeSH
• Enterocytes immunology   MeSH
• Macrophages immunology   MeSH
• Mast Cells immunology   MeSH
• Inflammation Mediators metabolism   MeSH
• Mice MeSH
• Neutrophils immunology   MeSH
• Salmonella typhimurium * MeSH
• Salmonella Infections, Animal immunology   microbiology   MeSH
• Intestines immunology   microbiology   MeSH
• T-Lymphocytes immunology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Cytokines MeSH
• Inflammation Mediators MeSH