Salmonella Typhimurium is an enteric pathogen that causes acute and chronic infections in humans and animals. One-week-old germ-free piglets were orally colonized/infected with the Salmonella Typhimurium LT2 strain or its isogenic rough ΔrfaL, ΔrfaG or ΔrfaC mutants with exactly defined lipopolysaccharide (LPS) defects. After 24 h, the piglets were euthanized and the colonization of the small intestine, translocations into the mesenteric lymph nodes, liver, spleen, lungs, and bacteremia, along with changes in the ileum histology, and transcription levels of the tight junction proteins claudin-1, claudin-2, and occludin were all assessed. Additionally, transcription levels of IL-8, TNF-α, and IL-10 in the terminal ileum, and their local and systemic protein levels were evaluated. Wild-type Salmonella Typhimurium showed the highest translocation, histopathological changes, upregulation of claudins and downregulation of occludin, transcription of the cytokines, intestinal IL-8 and TNF-α levels, and systemic TNF-α and IL-10 levels. Depending on the extent of the incompleteness of the LPS, the levels of the respective elements decreased, or no changes were observed at all in the piglets colonized/infected with Δrfa mutants. Intestinal IL-10 and systemic IL-8 levels were not detected in any piglet groups. This study provided foundational data on the gnotobiotic piglet response to colonization/infection with the exactly defined rough Salmonella Typhimurium LT2 isogenic mutants.

• Keywords
• Salmonella Typhimurium, cytokines, germ-free piglet, gnotobiotic, lipopolysaccharide, tight junction proteins, Δrfa mutant,
• MeSH
• Cytokines immunology   MeSH
• Germ-Free Life * MeSH
• Liver microbiology   MeSH
• Lipopolysaccharides toxicity   MeSH
• Lymph Nodes microbiology   MeSH
• Mutation MeSH
• Lung microbiology   MeSH
• Swine MeSH
• Salmonella typhimurium genetics   physiology   MeSH
• Salmonella Infections immunology   microbiology   pathology   MeSH
• Spleen microbiology   MeSH
• Intestine, Small immunology   microbiology   pathology   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
• Cytokines MeSH
• Lipopolysaccharides 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

One-week-old breast-fed miniature piglets were orally infected either with virulent LT2 strain or with a non-virulent SF1591 rough mutant of Salmonella Typhimurium for 1 d. Both microorganisms were cultivated from mesenteric lymph nodes but not from the blood of infected piglets. Interleukins (IL) 1 beta, 8, 18, tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) were quantified by ELISA in plasma and washes of a terminal part of the small bowel. In plasma, cytokines were mostly missing in non-infected piglets and either missing or low in infected piglets. In the gut of non-infected piglets, IL-1 beta, IL-8 and IL-18 were detected whereas TNF-alpha and IFN-gamma were mostly missing. IFN-gamma levels highly increased (p < 0.05) after infection with nonvirulent salmonellae. The variability of cytokine levels in the gut of suckling piglets is discussed.

• MeSH
• Cytokines blood   metabolism   MeSH
• Microscopy, Electron veterinary   MeSH
• Enzyme-Linked Immunosorbent Assay veterinary   MeSH
• Gastrointestinal Diseases immunology   microbiology   pathology   veterinary   MeSH
• Ileum immunology   microbiology   pathology   ultrastructure   MeSH
• Lymph Nodes immunology   microbiology   pathology   ultrastructure   MeSH
• Swine, Miniature MeSH
• Swine Diseases immunology   microbiology   pathology   MeSH
• Animals, Newborn MeSH
• Swine MeSH
• Salmonella typhimurium growth & development   ultrastructure   MeSH
• Salmonella Infections, Animal immunology   microbiology   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Cytokines 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

The germ-free pig model is shown to be useful for studying salmonellosis. The immune status of germ-free and infected gnotobiotic piglets is described. The regulatory role of cytokine is discussed and compared with our experimental findings.

• MeSH
• B-Lymphocytes microbiology   MeSH
• Immunoglobulin A blood   MeSH
• Immunoglobulin G blood   MeSH
• Immunoglobulin M blood   MeSH
• Interferon-gamma blood   MeSH
• Disease Models, Animal * MeSH
• Specific Pathogen-Free Organisms MeSH
• Swine * MeSH
• Antibodies, Bacterial blood   MeSH
• Salmonella typhimurium immunology   MeSH
• Salmonella Infections, Animal immunology   microbiology   MeSH
• Tumor Necrosis Factor-alpha metabolism   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Immunoglobulin A MeSH
• Immunoglobulin G MeSH
• Immunoglobulin M MeSH
• Interferon-gamma MeSH
• Antibodies, Bacterial MeSH
• Tumor Necrosis Factor-alpha MeSH

Two stable rough mutants of Salmonella spp. were studied as live peroral vaccines. The SF1591 mutant of S. typhimurium (Ra chemotype) protected germ-free piglets against subsequent infection with virulent smooth S. typhimurium LT2, whereas a deep-rough mutant of S. minnesota mR595 (Re chemotype) did not. We investigated cytokine and leukocyte profiles in the ilea of gnotobiotic piglets colonized for 1 week either with rough mutants alone or with rough mutants followed by S. typhimurium LT2. The ileal mucosae of piglets associated with strain SF1591 alone were not inflamed. Villi contained activated macrophages, and enterocytes expressed transforming growth factor beta (TGF-beta). Subsequent infection of piglets with S. typhimurium LT2 resulted in immigration of alphabeta T cells and immunoglobulin A (IgA) response. In contrast, the ileal mucosae of piglets associated with strain mR595 alone expressed heat shock proteins and inflammatory cytokines but not TGF-beta. Acellular villi contained numerous gammadelta T cells but no alphabeta T cells. After subsequent challenge with the LT2 strain, most piglets died of sepsis. Intestinal mucosae contained IgG but no IgA. These findings suggest the importance of cytokine signals in the regulation of intestinal responses against Salmonella infection.

• MeSH
• Cytokines immunology   MeSH
• Germ-Free Life * MeSH
• Ileum immunology   microbiology   pathology   MeSH
• Swine, Miniature MeSH
• Swine MeSH
• Salmonella typhimurium * MeSH
• Salmonella Infections, Animal immunology   pathology   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