Nejvíce citovaný článek - PubMed ID 10069015
Salmonellosis: lessons drawn from a germ-free pig model
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
- bakteriální infekce krev imunologie mikrobiologie MeSH
- biologické markery krev MeSH
- ELISA MeSH
- Escherichia coli růst a vývoj MeSH
- gnotobiologické modely * MeSH
- ileum metabolismus mikrobiologie MeSH
- interleukin-10 krev MeSH
- interleukin-8 krev MeSH
- modely nemocí na zvířatech MeSH
- novorozená zvířata krev imunologie mikrobiologie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- prasata MeSH
- protein HMGB1 * krev MeSH
- průjem MeSH
- Salmonella typhimurium růst a vývoj MeSH
- sepse krev imunologie mikrobiologie MeSH
- stupeň závažnosti nemoci MeSH
- tachykardie MeSH
- TNF-alfa krev MeSH
- tremor MeSH
- zánět krev imunologie mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- interleukin-10 MeSH
- interleukin-8 MeSH
- protein HMGB1 * MeSH
- TNF-alfa 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
- antibióza * MeSH
- Bifidobacterium imunologie MeSH
- cytokiny analýza krev MeSH
- Escherichia coli imunologie MeSH
- gnotobiologické modely MeSH
- ileum imunologie mikrobiologie MeSH
- kolon imunologie mikrobiologie MeSH
- prasata MeSH
- probiotika terapeutické užití MeSH
- Salmonella typhimurium imunologie MeSH
- salmonelová infekce u zvířat imunologie terapie MeSH
- střeva imunologie mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cytokiny 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
- gastrointestinální trakt imunologie MeSH
- lidé MeSH
- přirozená imunita * MeSH
- Salmonella imunologie MeSH
- salmonelóza imunologie MeSH
- slizniční imunita * MeSH
- střevní sliznice imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy 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
- elektronová mikroskopie MeSH
- fagocytóza MeSH
- gnotobiologické modely MeSH
- imunoenzymatické techniky MeSH
- játra ultrastruktura MeSH
- lymfatické uzliny metabolismus ultrastruktura MeSH
- mezenterium MeSH
- miniaturní prasata MeSH
- oxid dusnatý metabolismus MeSH
- plíce ultrastruktura MeSH
- prasata MeSH
- Salmonella typhimurium patogenita MeSH
- salmonelová infekce u zvířat imunologie metabolismus mikrobiologie patologie MeSH
- střeva ultrastruktura MeSH
- tyrosin analogy a deriváty metabolismus MeSH
- virulence MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 3-nitrotyrosine MeSH Prohlížeč
- oxid dusnatý MeSH
- tyrosin 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
- cytokiny biosyntéza MeSH
- enterocyty imunologie MeSH
- makrofágy imunologie MeSH
- mastocyty imunologie MeSH
- mediátory zánětu metabolismus MeSH
- myši MeSH
- neutrofily imunologie MeSH
- Salmonella typhimurium * MeSH
- salmonelová infekce u zvířat imunologie mikrobiologie MeSH
- střeva imunologie mikrobiologie MeSH
- T-lymfocyty imunologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cytokiny MeSH
- mediátory zánětu MeSH