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Infect Immun. Jun 1995; 63(6): 2302–2309.
PMCID: PMC173301

Transepithelial signaling to neutrophils by salmonellae: a novel virulence mechanism for gastroenteritis.

Abstract

Salmonella serotypes which elicit human enteritis cannot be distinguished from those that do not on the basis of their in vitro interactions with eukaryotic cells. We have recently reported that an enteritis-producing strain of Salmonella typhimurium signals intact intestinal epithelium to recruit subepithelial neutrophils to migrate across the epithelial (B. A. McCormick, S. P. Colgan, C. D. Archer, S. I. Miller, and J. L. Madara, J. Cell Biol. 123:895-907, 1993). We now utilize a cell culture model of human intestinal epithelium (with T84 cells) to examine whether such transepithelial signaling to neutrophils by salmonellae is predictive of potential to elicit gastroenteritis. Various Salmonella serotypes, including S. typhimurium, S. enteritidis, S. pullorum, S. arizonae, S. typhi, and S. paratyphi, as well as invasion-defective mutants of S. typhimurium, were studied. Strains or serotypes which elicit diffuse enteritis in humans (defined histologically as transepithelial migration of neutrophils) exhibited transepithelial signaling to neutorphils across epithelial cell monolayers, while those which do not elicit diffuse enteritis in humans did not display transepithelial signaling. In contrast, the ability to enter the apical surface of T84 cells did not differentiate strains or serotypes which induce diffuse enteritis from those which do not. These results strongly suggest that the ability of salmonellae to elicit transepithelial signaling to neutrophils is a key virulence mechanism underlying Salmonella-elicited enteritis.

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Selected References

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  • Behlau I, Miller SI. A PhoP-repressed gene promotes Salmonella typhimurium invasion of epithelial cells. J Bacteriol. 1993 Jul;175(14):4475–4484. [PMC free article] [PubMed]
  • Day DW, Mandal BK, Morson BC. The rectal biopsy appearances in Salmonella colitis. Histopathology. 1978 Mar;2(2):117–131. [PubMed]
  • Dharmsathaphorn K, Madara JL. Established intestinal cell lines as model systems for electrolyte transport studies. Methods Enzymol. 1990;192:354–389. [PubMed]
  • Eckmann L, Jung HC, Schürer-Maly C, Panja A, Morzycka-Wroblewska E, Kagnoff MF. Differential cytokine expression by human intestinal epithelial cell lines: regulated expression of interleukin 8. Gastroenterology. 1993 Dec;105(6):1689–1697. [PubMed]
  • Eckmann L, Kagnoff MF, Fierer J. Epithelial cells secrete the chemokine interleukin-8 in response to bacterial entry. Infect Immun. 1993 Nov;61(11):4569–4574. [PMC free article] [PubMed]
  • Finlay BB, Falkow S. Salmonella interactions with polarized human intestinal Caco-2 epithelial cells. J Infect Dis. 1990 Nov;162(5):1096–1106. [PubMed]
  • Francis CL, Starnbach MN, Falkow S. Morphological and cytoskeletal changes in epithelial cells occur immediately upon interaction with Salmonella typhimurium grown under low-oxygen conditions. Mol Microbiol. 1992 Nov;6(21):3077–3087. [PubMed]
  • Galán JE, Curtiss R., 3rd Expression of Salmonella typhimurium genes required for invasion is regulated by changes in DNA supercoiling. Infect Immun. 1990 Jun;58(6):1879–1885. [PMC free article] [PubMed]
  • Galán JE, Ginocchio C, Costeas P. Molecular and functional characterization of the Salmonella invasion gene invA: homology of InvA to members of a new protein family. J Bacteriol. 1992 Jul;174(13):4338–4349. [PMC free article] [PubMed]
  • Galán JE, Pace J, Hayman MJ. Involvement of the epidermal growth factor receptor in the invasion of cultured mammalian cells by Salmonella typhimurium. Nature. 1992 Jun 18;357(6379):588–589. [PubMed]
  • Gulig PA, Curtiss R., 3rd Plasmid-associated virulence of Salmonella typhimurium. Infect Immun. 1987 Dec;55(12):2891–2901. [PMC free article] [PubMed]
  • Hornick RB, Greisman SE, Woodward TE, DuPont HL, Dawkins AT, Snyder MJ. Typhoid fever: pathogenesis and immunologic control. N Engl J Med. 1970 Sep 24;283(13):686–691. [PubMed]
  • Kumar NB, Nostrant TT, Appelman HD. The histopathologic spectrum of acute self-limited colitis (acute infectious-type colitis). Am J Surg Pathol. 1982 Sep;6(6):523–529. [PubMed]
  • Lee CA, Jones BD, Falkow S. Identification of a Salmonella typhimurium invasion locus by selection for hyperinvasive mutants. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1847–1851. [PMC free article] [PubMed]
  • Lee CA, Falkow S. The ability of Salmonella to enter mammalian cells is affected by bacterial growth state. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4304–4308. [PMC free article] [PubMed]
  • Madara JL. Warner-Lambert/Parke-Davis Award lecture. Pathobiology of the intestinal epithelial barrier. Am J Pathol. 1990 Dec;137(6):1273–1281. [PMC free article] [PubMed]
  • Madara JL, Dharmsathaphorn K. Occluding junction structure-function relationships in a cultured epithelial monolayer. J Cell Biol. 1985 Dec;101(6):2124–2133. [PMC free article] [PubMed]
  • Madara JL, Stafford J, Barenberg D, Carlson S. Functional coupling of tight junctions and microfilaments in T84 monolayers. Am J Physiol. 1988 Mar;254(3 Pt 1):G416–G423. [PubMed]
  • MacBeth KJ, Lee CA. Prolonged inhibition of bacterial protein synthesis abolishes Salmonella invasion. Infect Immun. 1993 Apr;61(4):1544–1546. [PMC free article] [PubMed]
  • McCormick BA, Colgan SP, Delp-Archer C, Miller SI, Madara JL. Salmonella typhimurium attachment to human intestinal epithelial monolayers: transcellular signalling to subepithelial neutrophils. J Cell Biol. 1993 Nov;123(4):895–907. [PMC free article] [PubMed]
  • McGovern VJ, Slavutin LJ. Pathology of salmonella colitis. Am J Surg Pathol. 1979 Dec;3(6):483–490. [PubMed]
  • Miller SI. PhoP/PhoQ: macrophage-specific modulators of Salmonella virulence? Mol Microbiol. 1991 Sep;5(9):2073–2078. [PubMed]
  • Miller SI, Mekalanos JJ. Constitutive expression of the phoP regulon attenuates Salmonella virulence and survival within macrophages. J Bacteriol. 1990 May;172(5):2485–2490. [PMC free article] [PubMed]
  • Nash S, Parkos C, Nusrat A, Delp C, Madara JL. In vitro model of intestinal crypt abscess. A novel neutrophil-derived secretagogue activity. J Clin Invest. 1991 Apr;87(4):1474–1477. [PMC free article] [PubMed]
  • Nevola JJ, Stocker BA, Laux DC, Cohen PS. Colonization of the mouse intestine by an avirulent Salmonella typhimurium strain and its lipopolysaccharide-defective mutants. Infect Immun. 1985 Oct;50(1):152–159. [PMC free article] [PubMed]
  • Parkos CA, Colgan SP, Delp C, Arnaout MA, Madara JL. Neutrophil migration across a cultured epithelial monolayer elicits a biphasic resistance response representing sequential effects on transcellular and paracellular pathways. J Cell Biol. 1992 May;117(4):757–764. [PMC free article] [PubMed]
  • Parkos CA, Delp C, Arnaout MA, Madara JL. Neutrophil migration across a cultured intestinal epithelium. Dependence on a CD11b/CD18-mediated event and enhanced efficiency in physiological direction. J Clin Invest. 1991 Nov;88(5):1605–1612. [PMC free article] [PubMed]
  • Revel HR. Restriction of nonglucosylated T-even bacteriophage: properties of permissive mutants of Escherichia coli B and K12. Virology. 1967 Apr;31(4):688–701. [PubMed]
  • Miller VL, Bliska JB, Falkow S. Nucleotide sequence of the Yersinia enterocolitica ail gene and characterization of the Ail protein product. J Bacteriol. 1990 Feb;172(2):1062–1069. [PMC free article] [PubMed]
  • Tacket CO, Hone DM, Curtiss R, 3rd, Kelly SM, Losonsky G, Guers L, Harris AM, Edelman R, Levine MM. Comparison of the safety and immunogenicity of delta aroC delta aroD and delta cya delta crp Salmonella typhi strains in adult volunteers. Infect Immun. 1992 Feb;60(2):536–541. [PMC free article] [PubMed]
  • Takeuchi A. Electron microscope studies of experimental Salmonella infection. I. Penetration into the intestinal epithelium by Salmonella typhimurium. Am J Pathol. 1967 Jan;50(1):109–136. [PMC free article] [PubMed]

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