Chickens can be infected with Salmonella enterica at any time during their life. However, infections within the first hours and days of their life are epidemiologically the most important, as newly hatched chickens are highly sensitive to Salmonella infection. Salmonella is initially recognized in the chicken caecum by TLR receptors and this recognition is followed by induction of chemokines, cytokines and many effector genes. This results in infiltration of heterophils, macrophages, B- and T-lymphocytes and changes in total gene expression in the caecal lamina propria. The highest induction in expression is observed for matrix metalloproteinase 7 (MMP7). Expression of this gene is increased in the chicken caecum over 4000 fold during the first 10 days after the infection of newly hatched chickens. Additional highly inducible genes in the caecum following S. Enteritidis infection include immune responsive gene 1 (IRG1), serum amyloid A (SAA), extracellular fatty acid binding protein (ExFABP), serine protease inhibitor (SERPINB10), trappin 6-like (TRAP6), calprotectin (MRP126), mitochondrial ES1 protein homolog (ES1), interferon-induced protein with tetratricopeptide repeats 5 (IFIT5), avidin (AVD) and transglutaminase 4 (TGM4). The induction of expression of these proteins exceeds a factor of 50. Similar induction rates are also observed for chemokines and cytokines such as IL1β, IL6, IL8, IL17, IL18, IL22, IFNγ, AH221 or iNOS. Once the infection is under control, which happens approx. 2 weeks after infection, expression of IgY and IgA increases to facilitate Salmonella elimination from the gut lumen. This review outlines the function of individual proteins expressed in chickens after infection with non-typhoid Salmonella serovars.

• MeSH
• Cecum metabolism   MeSH
• Gene Expression * MeSH
• Chickens * MeSH
• Poultry Diseases genetics   microbiology   MeSH
• Avian Proteins genetics   metabolism   MeSH
• Salmonella physiology   MeSH
• Salmonella Infections, Animal genetics   immunology   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Avian Proteins MeSH

The characterization of the immune response of chickens to Salmonella infection is usually limited to the quantification of expression of genes coding for cytokines, chemokines or antimicrobial peptides. However, processes occurring in the cecum of infected chickens are likely to be much more diverse. In this study we have therefore characterized the transcriptome and proteome in the chicken cecum after infection with Salmonella Enteritidis. Using a combination of 454 pyrosequencing, protein mass spectrometry and quantitative real-time PCR, we identified 48 down- and 56 up-regulated chicken genes after Salmonella Enteritidis infection. The most inducible gene was that coding for MMP7, exhibiting a 5952 fold induction 9 days post-infection. An induction of greater than 100 fold was observed for IgG, IRG1, SAA, ExFABP, IL-22, TRAP6, MRP126, IFNγ, iNOS, ES1, IL-1β, LYG2, IFIT5, IL-17, AVD, AH221 and SERPIN B. Since prostaglandin D2 synthase was upregulated and degrading hydroxyprostaglandin dehydrogenase was downregulated after the infection, prostaglandin must accumulate in the cecum of chickens infected with Salmonella Enteritidis. Finally, above mentioned signaling was dependent on the presence of a SPI1-encoded type III secretion system in Salmonella Enteritidis. The inflammation lasted for 2 weeks after which time the expression of the "inflammatory" genes returned back to basal levels and, instead, the expression of IgA and IgG increased. This points to an important role for immunoglobulins in the restoration of homeostasis in the cecum after infection.

• MeSH
• Cecum immunology   metabolism   MeSH
• Mass Spectrometry veterinary   MeSH
• Chickens * MeSH
• Poultry Diseases genetics   immunology   microbiology   MeSH
• Mouth Diseases genetics   immunology   microbiology   veterinary   MeSH
• Blotting, Northern veterinary   MeSH
• Polymerase Chain Reaction veterinary   MeSH
• Immunity, Innate * MeSH
• Proteome immunology   MeSH
• Avian Proteins genetics   immunology   MeSH
• Gene Expression Regulation * MeSH
• Salmonella enteritidis immunology   MeSH
• Salmonella Infections, Animal genetics   immunology   microbiology   MeSH
• Sequence Analysis, DNA veterinary   MeSH
• Transcriptome MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Proteome MeSH
• Avian Proteins MeSH

Genes localized at Salmonella pathogenicity island-1 (SPI-1) are involved in Salmonella enterica invasion of host non-professional phagocytes. Interestingly, in macrophages, SPI-1-encoded proteins, in addition to invasion, induce cell death via activation of caspase-1 which also cleaves proIL-1β and proIL-18, precursors of 2 proinflammatory cytokines. In this study we were therefore interested in whether SPI-1-encoded type III secretion system (T3SS) may influence proinflammatory response of macrophages. To test this hypothesis, we infected primary porcine alveolar macrophages with wild-type S. Typhimurium and S. Enteritidis and their isogenic SPI-1 deletion mutants. ΔSPI1 mutants of both serovars invaded approx. 5 times less efficiently than the wild-type strains and despite this, macrophages responded to the infection with ΔSPI1 mutants by increased expression of proinflammatory cytokines IL-1β, IL-8, TNFα, IL-23α and GM-CSF. Identical macrophage responses to that induced by the ΔSPI1 mutants were also observed to the infection with sipB but not the sipA mutant. The hilA mutant exhibited an intermediate phenotype between the ΔSPI1 mutant and the wild-type S. Enteritidis. Our results showed that the SPI-1-encoded T3SS is required not only for cell invasion but in macrophages also for the suppression of early proinflammatory cytokine expression.

• MeSH
• Macrophages, Alveolar immunology   metabolism   MeSH
• Cytokines genetics   metabolism   MeSH
• Genomic Islands * MeSH
• Swine Diseases immunology   microbiology   MeSH
• Swine MeSH
• Salmonella enteritidis genetics   MeSH
• Salmonella typhimurium genetics   metabolism   MeSH
• Salmonella Infections, Animal 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

BACKGROUND: In this study we were interested in the colonisation and early immune response of Balb/C mice to infection with Salmonella Enteritidis and isogenic pathogenicity island free mutants. RESULTS: The virulence of S. Enteritidis for Balb/C mice was exclusively dependent on intact SPI-2. Infections with any of the mutants harbouring SPI-2 (including the mutant in which we left only SPI-2 but removed SPI-1, SPI-3, SPI-4 and SPI-5) resulted in fatalities, liver injures and NK cell depletion from the spleen. The infection was of minimal influence on counts of splenic CD4 CD8 T lymphocytes and gammadelta T-lymphocytes although a reduced ability of splenic lymphocytes to respond to non-specific mitogens indicated general immunosuppression in mice infected with SPI-2 positive S. Enteritidis mutants. Further investigations showed that NK cells were depleted also in blood but not in the caecal lamina propria. However, NK cell depletion was not directly associated with the presence of SPI-2 and was rather an indicator of virulence or avirulence of a particular mutant because the depletion was not observed in mice infected with other attenuated mutants such as lon and rfaL. CONCLUSIONS: The virulence of S. Enteritidis for Balb/C mice is exclusively dependent on the presence of SPI-2 in its genome, and a major hallmark of the infection in terms of early changes in lymphocyte populations is the depletion of NK cells in spleen and blood. The decrease of NK cells in circulation can be used as a marker of attenuation of S. Enteritidis mutants for Balb/C mice.

• MeSH
• Antigens, CD19 immunology   MeSH
• CD3 Complex immunology   MeSH
• Bacterial Proteins genetics   immunology   MeSH
• Killer Cells, Natural immunology   MeSH
• Cytokines immunology   MeSH
• Histocytochemistry MeSH
• Lymphocytes cytology   immunology   MeSH
• Membrane Proteins genetics   immunology   MeSH
• Disease Models, Animal MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• Statistics, Nonparametric MeSH
• Cell Proliferation MeSH
• Salmonella enteritidis genetics   pathogenicity   MeSH
• Salmonella Infections, Animal immunology   microbiology   MeSH
• Virulence MeSH
• Bacterial Shedding 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
• Antigens, CD19 MeSH
• CD3 Complex MeSH
• Bacterial Proteins MeSH
• Cytokines MeSH
• Membrane Proteins MeSH
• SPI-2 protein, Salmonella MeSH Browser
• Spi1 protein, Salmonella MeSH Browser

BACKGROUND: Salmonella is a highly successful parasite of reptiles, birds and mammals. Its ability to infect and colonise such a broad range of hosts coincided with the introduction of new genetic determinants, among them 5 major pathogenicity islands (SPI1-5), into the Salmonella genome. However, only limited information is available on how each of these pathogenicity islands influences the ability of Salmonella to infect chickens. In this study, we therefore constructed Salmonella Enteritidis mutants with each SPI deleted separately, with single individual SPIs (i.e. with the remaining four deleted) and a mutant with all 5 SPIs deleted, and assessed their virulence in one-day-old chickens, together with the innate immune response of this host. RESULTS: The mutant lacking all 5 major SPIs was still capable of colonising the caecum while colonisation of the liver and spleen was dependent on the presence of both SPI-1 and SPI-2. In contrast, the absence of SPI-3, SPI-4 or SPI-5 individually did not influence virulence of S. Enteritidis for chickens, but collectively they contributed to the colonisation of the spleen. Proinflammatory signalling and heterophil infiltration was dependent on intact SPI-1 only and not on other SPIs. CONCLUSIONS: SPI-1 and SPI-2 are the two most important pathogenicity islands of Salmonella Enteritidis required for the colonisation of systemic sites in chickens.

• MeSH
• RNA, Bacterial genetics   MeSH
• Genomic Islands * MeSH
• Chickens immunology   microbiology   MeSH
• Poultry Diseases immunology   microbiology   MeSH
• Immunity, Innate MeSH
• Salmonella enteritidis genetics   pathogenicity   MeSH
• Salmonella Infections, Animal immunology   microbiology   MeSH
• Sequence Deletion MeSH
• Virulence MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH
• Names of Substances
• RNA, Bacterial MeSH

Using transcriptional promoter fusions, we investigated the expression of selected SPI-1 and SPI-2 genes of Salmonella enterica serovar Typhimurium (S. Typhimurium). Promoters of genes related to the invasion of the epithelial cell (hilA, hilC, hilD, invF, sicA, sopA, sopB and sopE2) were active in Luria-Bertani (LB) medium and LB with butyrate but were suppressed by bile salts and in glucose minimal (M9) medium. Genes related to S. Typhimurium intracellular survival (phoP, ssrA, ssaB, ssaG, sifA, sifB and pipB) were characterized by their expression in stationary phase in LB and M9 medium. Activity of phoP and ssrA promoters indicated that these might be expressed inside the gut. SPI-1 genes were expressed on the transition to stationary phase while SPI-2 genes were expressed in stationary phase. Among SPI-1 genes, those with regulatory functions preceded in expression the effector genes and sop genes were expressed in the order of sopA, sopB and sopE2, showing hierarchy in the expression of S. Typhimurium virulence genes.

• MeSH
• Genes, Bacterial genetics   MeSH
• Bacterial Proteins metabolism   MeSH
• Time Factors MeSH
• Glucose MeSH
• Culture Media MeSH
• Promoter Regions, Genetic genetics   MeSH
• Gene Expression Regulation, Bacterial * MeSH
• Salmonella typhimurium genetics   growth & development   pathogenicity   MeSH
• Salmonella Infections microbiology   MeSH
• Trans-Activators metabolism   MeSH
• Virulence genetics   MeSH
• Bile Acids and Salts MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Bacterial Proteins MeSH
• Glucose MeSH
• HilA protein, Salmonella MeSH Browser
• Culture Media MeSH
• Trans-Activators MeSH
• Bile Acids and Salts MeSH