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. 1996 Dec;64(12):5357–5365. doi: 10.1128/iai.64.12.5357-5365.1996

In vivo apoptosis in Shigella flexneri infections.

A Zychlinsky 1, K Thirumalai 1, J Arondel 1, J R Cantey 1, A O Aliprantis 1, P J Sansonetti 1
PMCID: PMC174530  PMID: 8945588

Abstract

Shigella flexneri, an etiological agent of bacillary dysentery, causes apoptosis in vitro. Here we show that it also induces apoptosis in vivo. We were able to quantify the number of apoptotic cells in rabbit Peyer's patches infected with S. flexneri by detecting cells with fragmented DNA. Infection with virulent S. flexneri results in massive numbers of apoptotic cells within the lymphoid follicles. In contrast, neither an avirulent strain nor an avirulent strain capable of colonizing Peyer's patches increases the background level of apoptotic cells. Macrophages, T cells, and B cells are shown to undergo apoptosis in vivo. These results indicate that apoptosis may play a crucial role in the pathogenesis of shigellosis.

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Selected References

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  1. Alvarez-Buylla A., Vicario D. S. Simple microcomputer system for mapping tissue sections with the light microscope. J Neurosci Methods. 1988 Sep;25(2):165–173. doi: 10.1016/0165-0270(88)90155-0. [DOI] [PubMed] [Google Scholar]
  2. Anand B. S., Malhotra V., Bhattacharya S. K., Datta P., Datta D., Sen D., Bhattacharya M. K., Mukherjee P. P., Pal S. C. Rectal histology in acute bacillary dysentery. Gastroenterology. 1986 Mar;90(3):654–660. doi: 10.1016/0016-5085(86)91120-0. [DOI] [PubMed] [Google Scholar]
  3. Arends M. J., Wyllie A. H. Apoptosis: mechanisms and roles in pathology. Int Rev Exp Pathol. 1991;32:223–254. doi: 10.1016/b978-0-12-364932-4.50010-1. [DOI] [PubMed] [Google Scholar]
  4. Cantey J. R., Blake R. K. Diarrhea due to Escherichia coli in the rabbit: a novel mechanism. J Infect Dis. 1977 Mar;135(3):454–462. doi: 10.1093/infdis/135.3.454. [DOI] [PubMed] [Google Scholar]
  5. Cheney C. P., Formal S. B., Schad P. A., Boedeker E. C. Genetic transfer of a mucosal adherence factor (R1) from an enteropathogenic Escherichia coli strain into a Shigella flexneri strain and the phenotypic suppression of this adherence factor. J Infect Dis. 1983 Apr;147(4):711–723. doi: 10.1093/infdis/147.4.711. [DOI] [PubMed] [Google Scholar]
  6. Clerc P. L., Ryter A., Mounier J., Sansonetti P. J. Plasmid-mediated early killing of eucaryotic cells by Shigella flexneri as studied by infection of J774 macrophages. Infect Immun. 1987 Mar;55(3):521–527. doi: 10.1128/iai.55.3.521-527.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ellis R. E., Yuan J. Y., Horvitz H. R. Mechanisms and functions of cell death. Annu Rev Cell Biol. 1991;7:663–698. doi: 10.1146/annurev.cb.07.110191.003311. [DOI] [PubMed] [Google Scholar]
  8. Gavrieli Y., Sherman Y., Ben-Sasson S. A. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol. 1992 Nov;119(3):493–501. doi: 10.1083/jcb.119.3.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Inman L. R., Cantey J. R. Peyer's patch lymphoid follicle epithelial adherence of a rabbit enteropathogenic Escherichia coli (strain RDEC-1). Role of plasmid-mediated pili in initial adherence. J Clin Invest. 1984 Jul;74(1):90–95. doi: 10.1172/JCI111423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kraehenbuhl J. P., Neutra M. R. Molecular and cellular basis of immune protection of mucosal surfaces. Physiol Rev. 1992 Oct;72(4):853–879. doi: 10.1152/physrev.1992.72.4.853. [DOI] [PubMed] [Google Scholar]
  11. Mathan M. M., Mathan V. I. Morphology of rectal mucosa of patients with shigellosis. Rev Infect Dis. 1991 Mar-Apr;13 (Suppl 4):S314–S318. doi: 10.1093/clinids/13.supplement_4.s314. [DOI] [PubMed] [Google Scholar]
  12. Maurelli A. T., Sansonetti P. J. Genetic determinants of Shigella pathogenicity. Annu Rev Microbiol. 1988;42:127–150. doi: 10.1146/annurev.mi.42.100188.001015. [DOI] [PubMed] [Google Scholar]
  13. Perdomo O. J., Cavaillon J. M., Huerre M., Ohayon H., Gounon P., Sansonetti P. J. Acute inflammation causes epithelial invasion and mucosal destruction in experimental shigellosis. J Exp Med. 1994 Oct 1;180(4):1307–1319. doi: 10.1084/jem.180.4.1307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sansonetti P. J., Arondel J., Cantey J. R., Prévost M. C., Huerre M. Infection of rabbit Peyer's patches by Shigella flexneri: effect of adhesive or invasive bacterial phenotypes on follicle-associated epithelium. Infect Immun. 1996 Jul;64(7):2752–2764. doi: 10.1128/iai.64.7.2752-2764.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Sansonetti P. J., Arondel J., Cavaillon J. M., Huerre M. Role of interleukin-1 in the pathogenesis of experimental shigellosis. J Clin Invest. 1995 Aug;96(2):884–892. doi: 10.1172/JCI118135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Sansonetti P. J., Arondel J. Construction and evaluation of a double mutant of Shigella flexneri as a candidate for oral vaccination against shigellosis. Vaccine. 1989 Oct;7(5):443–450. doi: 10.1016/0264-410x(89)90160-6. [DOI] [PubMed] [Google Scholar]
  17. Sansonetti P. J., Hale T. L., Dammin G. J., Kapfer C., Collins H. H., Jr, Formal S. B. Alterations in the pathogenicity of Escherichia coli K-12 after transfer of plasmid and chromosomal genes from Shigella flexneri. Infect Immun. 1983 Mar;39(3):1392–1402. doi: 10.1128/iai.39.3.1392-1402.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sansonetti P. J., Kopecko D. J., Formal S. B. Involvement of a plasmid in the invasive ability of Shigella flexneri. Infect Immun. 1982 Mar;35(3):852–860. doi: 10.1128/iai.35.3.852-860.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Tsukada T., Rosenfeld M., Ross R., Gown A. M. Immunocytochemical analysis of cellular components in atherosclerotic lesions. Use of monoclonal antibodies with the Watanabe and fat-fed rabbit. Arteriosclerosis. 1986 Nov-Dec;6(6):601–613. doi: 10.1161/01.atv.6.6.601. [DOI] [PubMed] [Google Scholar]
  20. Wassef J. S., Keren D. F., Mailloux J. L. Role of M cells in initial antigen uptake and in ulcer formation in the rabbit intestinal loop model of shigellosis. Infect Immun. 1989 Mar;57(3):858–863. doi: 10.1128/iai.57.3.858-863.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Zychlinsky A., Fitting C., Cavaillon J. M., Sansonetti P. J. Interleukin 1 is released by murine macrophages during apoptosis induced by Shigella flexneri. J Clin Invest. 1994 Sep;94(3):1328–1332. doi: 10.1172/JCI117452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Zychlinsky A., Kenny B., Ménard R., Prévost M. C., Holland I. B., Sansonetti P. J. IpaB mediates macrophage apoptosis induced by Shigella flexneri. Mol Microbiol. 1994 Feb;11(4):619–627. doi: 10.1111/j.1365-2958.1994.tb00341.x. [DOI] [PubMed] [Google Scholar]
  23. Zychlinsky A., Perdomo J. J., Sansonetti P. J. Molecular and cellular mechanisms of tissue invasion by Shigella flexneri. Ann N Y Acad Sci. 1994 Aug 15;730:197–208. doi: 10.1111/j.1749-6632.1994.tb44249.x. [DOI] [PubMed] [Google Scholar]
  24. Zychlinsky A., Prevost M. C., Sansonetti P. J. Shigella flexneri induces apoptosis in infected macrophages. Nature. 1992 Jul 9;358(6382):167–169. doi: 10.1038/358167a0. [DOI] [PubMed] [Google Scholar]

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