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Salmonella-induced mucosal lectin RegIIIβ kills competing gut microbiota.

Stelter C, Käppeli R, König C, Krah A, Hardt WD, Stecher B, Bumann D - PLoS ONE (2011)

Bottom Line: Co-infection experiments with an avirulent S.Typhimurium mutant and a RegIIIβ-sensitive commensal E. coli strain demonstrated that feeding of RegIIIβ was sufficient for suppressing commensals in the absence of all other changes inflicted by mucosal disease.These data suggest that RegIIIβ production by the host can promote S.

View Article: PubMed Central - PubMed

Affiliation: Junior Group, Mucosal Infections, Institute of Immunology, Hannover Medical School, Hannover, Germany.

ABSTRACT
Intestinal inflammation induces alterations of the gut microbiota and promotes overgrowth of the enteric pathogen Salmonella enterica by largely unknown mechanisms. Here, we identified a host factor involved in this process. Specifically, the C-type lectin RegIIIβ is strongly upregulated during mucosal infection and released into the gut lumen. In vitro, RegIIIβ kills diverse commensal gut bacteria but not Salmonella enterica subspecies I serovar Typhimurium (S. Typhimurium). Protection of the pathogen was attributable to its specific cell envelope structure. Co-infection experiments with an avirulent S. Typhimurium mutant and a RegIIIβ-sensitive commensal E. coli strain demonstrated that feeding of RegIIIβ was sufficient for suppressing commensals in the absence of all other changes inflicted by mucosal disease. These data suggest that RegIIIβ production by the host can promote S. Typhimurium infection by eliminating inhibitory gut microbiota.

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S. Typhimurium-induced RegIIIβ expression in mouse intestine.A) RegIIIβ expression was analyzed in the cecum of streptomycin-treated C57BL/6 mice infected for 24 h with S. Typhimurium wt and S. Typhimurium avir, respectively. Expression was analyzed by quantitative real time PCR normalized to GAPDH mRNA levels (fold expression versus unmanipulated mouse). B) Western Blot of intestinal contents obtained from S. Typhimurium infected MyD88+/− and MyD88−/− litter mates 24 h post infection using a polyclonal antibody to RegIIIβ. Samples 1–3 were obtained from infected MyD88+/− mice and samples 4–6 from MyD88−/− litter mates. C) Immunohistochemistry of the cecal mucosa of S. Typhimurium infected mice 24 h post infection (grey, nuclei (DAPI); blue, actin (phalloidin); red, RegIIIβ). Scale bar: 10 µm.
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pone-0020749-g001: S. Typhimurium-induced RegIIIβ expression in mouse intestine.A) RegIIIβ expression was analyzed in the cecum of streptomycin-treated C57BL/6 mice infected for 24 h with S. Typhimurium wt and S. Typhimurium avir, respectively. Expression was analyzed by quantitative real time PCR normalized to GAPDH mRNA levels (fold expression versus unmanipulated mouse). B) Western Blot of intestinal contents obtained from S. Typhimurium infected MyD88+/− and MyD88−/− litter mates 24 h post infection using a polyclonal antibody to RegIIIβ. Samples 1–3 were obtained from infected MyD88+/− mice and samples 4–6 from MyD88−/− litter mates. C) Immunohistochemistry of the cecal mucosa of S. Typhimurium infected mice 24 h post infection (grey, nuclei (DAPI); blue, actin (phalloidin); red, RegIIIβ). Scale bar: 10 µm.

Mentions: All S. Typhimurium strains used in this study were derivatives of SL1344 hisG rpsL xyl [32] (TABLE 1). The virulent and avirulent S. Typhimurium strains have been described previously [33], [34] as well as S. Typhimurium ΔaroA [35]. Salmonella Typhimurium mutants with defined gene deletions were obtained using the Lambda phage red recombinase method [36] with primers described at http://falkow.stanford.edu/whatwedo/wanner/ (see also TABLE 2). For comparison of LPS defect mutants, Salmonella Typhimurium LT galE [37] was used.


Salmonella-induced mucosal lectin RegIIIβ kills competing gut microbiota.

Stelter C, Käppeli R, König C, Krah A, Hardt WD, Stecher B, Bumann D - PLoS ONE (2011)

S. Typhimurium-induced RegIIIβ expression in mouse intestine.A) RegIIIβ expression was analyzed in the cecum of streptomycin-treated C57BL/6 mice infected for 24 h with S. Typhimurium wt and S. Typhimurium avir, respectively. Expression was analyzed by quantitative real time PCR normalized to GAPDH mRNA levels (fold expression versus unmanipulated mouse). B) Western Blot of intestinal contents obtained from S. Typhimurium infected MyD88+/− and MyD88−/− litter mates 24 h post infection using a polyclonal antibody to RegIIIβ. Samples 1–3 were obtained from infected MyD88+/− mice and samples 4–6 from MyD88−/− litter mates. C) Immunohistochemistry of the cecal mucosa of S. Typhimurium infected mice 24 h post infection (grey, nuclei (DAPI); blue, actin (phalloidin); red, RegIIIβ). Scale bar: 10 µm.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3111430&req=5

pone-0020749-g001: S. Typhimurium-induced RegIIIβ expression in mouse intestine.A) RegIIIβ expression was analyzed in the cecum of streptomycin-treated C57BL/6 mice infected for 24 h with S. Typhimurium wt and S. Typhimurium avir, respectively. Expression was analyzed by quantitative real time PCR normalized to GAPDH mRNA levels (fold expression versus unmanipulated mouse). B) Western Blot of intestinal contents obtained from S. Typhimurium infected MyD88+/− and MyD88−/− litter mates 24 h post infection using a polyclonal antibody to RegIIIβ. Samples 1–3 were obtained from infected MyD88+/− mice and samples 4–6 from MyD88−/− litter mates. C) Immunohistochemistry of the cecal mucosa of S. Typhimurium infected mice 24 h post infection (grey, nuclei (DAPI); blue, actin (phalloidin); red, RegIIIβ). Scale bar: 10 µm.
Mentions: All S. Typhimurium strains used in this study were derivatives of SL1344 hisG rpsL xyl [32] (TABLE 1). The virulent and avirulent S. Typhimurium strains have been described previously [33], [34] as well as S. Typhimurium ΔaroA [35]. Salmonella Typhimurium mutants with defined gene deletions were obtained using the Lambda phage red recombinase method [36] with primers described at http://falkow.stanford.edu/whatwedo/wanner/ (see also TABLE 2). For comparison of LPS defect mutants, Salmonella Typhimurium LT galE [37] was used.

Bottom Line: Co-infection experiments with an avirulent S.Typhimurium mutant and a RegIIIβ-sensitive commensal E. coli strain demonstrated that feeding of RegIIIβ was sufficient for suppressing commensals in the absence of all other changes inflicted by mucosal disease.These data suggest that RegIIIβ production by the host can promote S.

View Article: PubMed Central - PubMed

Affiliation: Junior Group, Mucosal Infections, Institute of Immunology, Hannover Medical School, Hannover, Germany.

ABSTRACT
Intestinal inflammation induces alterations of the gut microbiota and promotes overgrowth of the enteric pathogen Salmonella enterica by largely unknown mechanisms. Here, we identified a host factor involved in this process. Specifically, the C-type lectin RegIIIβ is strongly upregulated during mucosal infection and released into the gut lumen. In vitro, RegIIIβ kills diverse commensal gut bacteria but not Salmonella enterica subspecies I serovar Typhimurium (S. Typhimurium). Protection of the pathogen was attributable to its specific cell envelope structure. Co-infection experiments with an avirulent S. Typhimurium mutant and a RegIIIβ-sensitive commensal E. coli strain demonstrated that feeding of RegIIIβ was sufficient for suppressing commensals in the absence of all other changes inflicted by mucosal disease. These data suggest that RegIIIβ production by the host can promote S. Typhimurium infection by eliminating inhibitory gut microbiota.

Show MeSH
Related in: MedlinePlus