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. 2005 Jul 27;108(5):1396–1404. doi: 10.1016/0016-5085(95)90687-8

Immunocytochemical evidence of Listeria, Escherichia coil, and Streptococcus antigens in Crohn's disease☆

Ying Liu ∗, Herbert J Van Kruiningen ∗,∗, ABrian West †, Richard W Cartun §, Antoine Cortot ∥, Jean-Frédéric Colombel ∥
PMCID: PMC7127655  PMID: 7729631

Abstract

Background/Aims Infectious agents have long been suspected of playing a role in the initiation of Crohn's disease. The objective of this study was to search for likely microbial agents in diseased tissues using immunocytochemical techniques. Methods Intestines and mesenteric lymph node specimens of 21 patients from two French families with a high frequency of Crohn's disease and from Connecticut were studied. The microbial agents searched for included Bacteroides vulgatus, Borrelia burgdorferi, Escherichia coil, Listeria monocytogenes, Streptococcus spp., bovine viral diarrhea virus, influenza A virus, measles virus, parainfluenza virus, and respiratory syncytial virus. Results Seventy-five percent of the patients with Crohn's disease (12 of 16) were positively labeled with the antibody to Listeria. Macrophages and giant cells immunolabeled for this antigen were distributed underneath ulcers, along fissures, around abscesses, within the lamina propria, in granulomas, and in the germinal centers of mesenteric lymph nodes. In addition, 57% (12 of 21) of the cases contained the E. coli antigen, and 44% (7 of 16) contained the streptococcal antigen. The immunolabeling for the latter two agents also occurred within macrophages and giant cells, distributed in a pattern similar to that of Listeria antigen. Conclusions The results suggest that Listeria spp., E. coli, and streptococci, but not measles virus, play a role in the pathogenesis of Crohn's disease.

Abbreviations: BVDV, bovine viral diarrhea virus; RSV, respiratory syncytial virus

Footnotes

☆

Supported partly by the Association F. Aupetit, the Caisse Régionale d'Assurance Maladie de Nord-Picardie, the Ministère de la Santé et de l'Action Humanitaire (Direction Générale de la Santé), the INSERM, and the Ferring Company.

References

  • 1.Crohn BB, Ginzburg L, Oppenheimer GD. Regional ileitis: a pathogenic and clinical entity. JAMA. 1932;99:1323–1328. [Google Scholar]
  • 2.Blaser MJ, Miller RA, Lacher J, Singleton JW. Patients with active Crohn's disease have elevated serum antibodies to antigens of seven enteric bacterial pathogens. Gastroenterology. 1984;87:888–894. [PubMed] [Google Scholar]
  • 3.Swarbrick ET, Kingham JGC, Price HL, Blackshaw AJ, Griffiths PD. Chlamydia, cytomegalovirus, and Yersinia in inflammatory bowel disease. Lancet. 1979;2:11–12. doi: 10.1016/s0140-6736(79)90176-4. [DOI] [PubMed] [Google Scholar]
  • 4.Blaser MJ, Hoverson D, Ely IG, Duncan DJ, Wang W-L, Brown WR. Studies of Campylobacter jejuni in patients with inflammatory bowel disease. Gastroenterology. 1984;86:33–38. [PubMed] [Google Scholar]
  • 5.Chiodini RJ, Van Kruiningen HJ, Thayer WR, Merkal RS, Coutu JA. Possible role of mycobacteria in inflammatory bowel disease. I. An unclassified Mycobacterium species isolated from patients with Crohn's disease. Dig Dis Sci. 1984;29:1073–1079. doi: 10.1007/BF01317078. [DOI] [PubMed] [Google Scholar]
  • 6.Sanderson JD, Moss MT, Tizard MLV, Hermon-Taylor J. Mycobacterium paratuberculosis DNA in Crohn's disease tissue. Gut. 1992;33:890–896. doi: 10.1136/gut.33.7.890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Van Kruiningen HJ, Chiodini RJ, Thayer WR, Coutu JA, Merkal RS, Runnels PL. Experimental disease in infant goats induced by Mycobacterium isolated from a patient with Crohn's disease. Dig Dis Sci. 1986;31:1351–1360. doi: 10.1007/BF01299814. [DOI] [PubMed] [Google Scholar]
  • 8.Wayne LG, Hollander D, Anderson B, Sramek HA, Vadheim CM, Rotter JI. Immunoglobulin A (IgA) and IgG serum antibodies to mycobacterial antigens in Crohn's disease patients and their relatives. J Clin Microbiol. 1992;30:2013–2018. doi: 10.1128/jcm.30.8.2013-2018.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Elliott PR, Forsey T, Darougar S, Treharne JD, Lennard-Jones JE. Chlamydiae and inflammatory bowel disease. Gut. 1981;22:25–27. doi: 10.1136/gut.22.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Schuller JL, Picket-van Ulsen J, Veeken IVD, Michel MF, Stoiz E. Antibodies against chlamydia of lymphogranuloma-venereum type in Crohn's disease. Lancet. 1979;1:19–20. doi: 10.1016/s0140-6736(79)90457-4. [DOI] [PubMed] [Google Scholar]
  • 11.Cartun RW, Van Kruiningen HJ, Pedersen CA, Berman MM. An immunocytochemical search for infectious agents in Crohn's disease. Modern Pathol. 1993;6:212–219. [PubMed] [Google Scholar]
  • 12.Wakefield AJ, Fox JD, Sawyerr AM, Taylor JE, Sweenie CH, Smith M, Emery VC, Hudson M, Tedder RS, Pounder RE. Detection of herpesvirus DNA in the large intestine of patients with ulcerative colitis and Crohn's disease using the nested polymerase chain reaction. J Med Virol. 1992;38:183–190. doi: 10.1002/jmv.1890380306. [DOI] [PubMed] [Google Scholar]
  • 13.Van Kruiningen HJ, Colombel JF, Cartun RW, Whitlock RH, Koopmans M, Kangro HO, Hoogkamp-Korstanje JAA, Lecomte-Houcke M, Devred M, Paris JC, Cortot A. An in-depth study of Crohn's disease in two French families. Gastroenterology. 1993;104:351–360. doi: 10.1016/0016-5085(93)90401-W. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Gump D. Lymphocytotoxic and microbial antibodies in Crohn's disease and matched controls. Antonie Van Leeuwenhoek. 1981;47:455–464. doi: 10.1007/BF00426006. [DOI] [PubMed] [Google Scholar]
  • 15.Breeling JL, Onderdonk AB, Cisneros RL. Bacteroides vulgatus outer membrane antigens associated with carrageenan-induced colitis in guinea pigs. Infect Immun. 1988;56:1754–1759. doi: 10.1128/iai.56.7.1754-1759.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Muller HE. Listeria isolations from feces of patients with diarrhea and from healthy food handlers. Infection. 1990;18:97–100. doi: 10.1007/BF01641423. [DOI] [PubMed] [Google Scholar]
  • 17.Heymer B, Wirsing von Konig CH, Finger H, Hof H, Emmeding P. Histomorphology of experimental listeriosis. Infection. 1988;16(Suppl 2):S106–S111. doi: 10.1007/BF01639731. [DOI] [PubMed] [Google Scholar]
  • 18.Gebauer K, Hall JC, Donlon JB, Herrmann R, Rofe S, Platell C. Hepatic involvement in listeriosis. Aust NZ J Med. 1989;19:486–487. doi: 10.1111/j.1445-5994.1989.tb00316.x. [DOI] [PubMed] [Google Scholar]
  • 19.Wakefield AJ, Sawyerr AM, Dhillon AP. Pathogenesis of Crohn's disease: multifocal gastrointestinal infarction. Lancet. 1989;2:1057–1062. doi: 10.1016/s0140-6736(89)91078-7. [DOI] [PubMed] [Google Scholar]
  • 20.Wakefield AJ, Sankey EA, Dhillon AP, Sawyerr AM, More L, Sim R, Pittilo RM, Rowles PM, Hudson M, Lewis AM, Pounder RE. Granulomatous vasculitis in Crohn's disease. Gastroenterology. 1991;100:1279–1287. [PubMed] [Google Scholar]
  • 21.Wakefield AJ, Pittilo RM, Cosby SL, Stephenson JR, Dhillon AP, Pounder RE. Evidence of persistent measles virus infection in Crohn's disease. J Med Virol. 1993;39:345–353. doi: 10.1002/jmv.1890390415. [DOI] [PubMed] [Google Scholar]
  • 22.Rickert RR, Carter HW. The “early” ulcerative lesion of Crohn's disease: correlative light- and scanning electron-microscopic studies. J Clin Gastroenterol. 1980;2:11–19. [PubMed] [Google Scholar]
  • 23.Rutgeerts P, Gboes K, Peeters M, Hiele M, Penninckx F, Aerts R, Kerremans R, Vantrappen G. Effect of faecal stream diversion on recurrence of Crohn's disease in the neoterminal ileum. Lancet. 1991;338:771–774. doi: 10.1016/0140-6736(91)90663-a. [DOI] [PubMed] [Google Scholar]
  • 24.Yolken R, Dubovi E, Leister F, Reid R, Almeido-Hill J, Santosham M. Infantile gastroenteritis associated with excretion of pestivirus antigens. Lancet. 1989;1:517–519. doi: 10.1016/s0140-6736(89)90066-4. [DOI] [PubMed] [Google Scholar]
  • 25.Ekbom A, Adami HO, Helmick CG, Jonzon A, Zack MM. Perinatal risk factors for inflammatory bowel disease: a case-control study. Am J Epidemiol. 1990;132:1111–1119. doi: 10.1093/oxfordjournals.aje.a115754. [DOI] [PubMed] [Google Scholar]
  • 26.Kangro HO, Chong SKF, Hardiman A, Heath RB, Walker-Smith JA. A prospective study of viral and mycoplasma infections in chronic inflammatory bowel disease. Gastroenterology. 1990;98:549–553. doi: 10.1016/0016-5085(90)90272-3. [DOI] [PubMed] [Google Scholar]
  • 27.Cartun RW, Pedersen CA. An immunocytochemical technique offering increased sensitivity and lowered cost with a streptavidinhorseradish peroxidase conjugate. J Histotechnol. 1989;12:273–277. [Google Scholar]
  • 28.Huang WM, Gibson SJ, Facer P, Gu J, Polak JM. Improved section adhesion for immunocytochemistry using high molecular weight polymers of l-lysine as a slide coating. Histochemistry. 1983;77:275–279. doi: 10.1007/BF00506570. [DOI] [PubMed] [Google Scholar]
  • 29.Rentrop M, Knapp B, Winter H, Schweizer J. Aminoalkylsilane-treated glass slides as support for in situ hybridization of keratin cDNA to frozen tissue sections under varying fixation and pretreatment conditions. Histochem J. 1986;18:271–276. doi: 10.1007/BF01676237. [DOI] [PubMed] [Google Scholar]
  • 30.Zachar Z, Savage DC. Microbial interference and colonization of the murine gastrointestinal tract by Listeria monocytogenes. Infect Immun. 1979;23:168–174. doi: 10.1128/iai.23.1.168-174.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.MacDonald TT, Carter PB. Cell-mediated immunity to intestinal infection. Infect Immun. 1980;28:516–523. doi: 10.1128/iai.28.2.516-523.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Brown WR, Lee E. Radioimmunological measurements of naturally occurring bacterial antibodies. I. Human serum antibodies reactive with Escherichia coli in gastrointestinal and immunologic disorders. J Lab Clin Med. 1973;82:125–136. [PubMed] [Google Scholar]
  • 33.Tabaqchali S, O'Donoghue DP, Bettelgeim KA. Escherichia coli antibodies in patients with inflammatory bowel disease. Gut. 1978;19:108–113. doi: 10.1136/gut.19.2.108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Ambrose NS, Johnson M, Burden DW, Keighly MRB. Incidence of pathogenic bacteria from mesenteric lymph nodes and ileal serosa during Crohn's disease. Br J Surg. 1984;71:623–625. doi: 10.1002/bjs.1800710821. [DOI] [PubMed] [Google Scholar]
  • 35.Sartor RB, Cromatie WJ, Powell DW, Schwab JH. Granulomatous entrocolitis induced in rats by purified bacterial cell wall fragments. Gastroenterology. 1985;89:587–595. doi: 10.1016/0016-5085(85)90455-x. [DOI] [PubMed] [Google Scholar]
  • 36.Hyzy J, Sciotti V, Albini B, Stinson M. Deposition of circulating streptococcal lipoteichoic acid in mouse tissues. Microb Pathog. 1992;13:123–132. doi: 10.1016/0882-4010(92)90072-v. [DOI] [PubMed] [Google Scholar]
  • 37.Fujinami RS, Oldstone MBA, Wroblewska Z, Frankel ME, Koprowski HK. 2nd ed. Vol. 80. 1983. Molecular mimicry in virus infection: crossreaction of measles virus phosphoprotein or of herpes simplex virus protein with human intermediate filaments; pp. 2346–2350. (Proc Natl Acad Sci USA). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Knibbs DR, Van Kruiningen HJ, Colombel JF, Cortot A. Ultrastructural evidence of paramyxovirus in two French families with Crohn's disease. Gastroenterology. 1993;104:A726. (abstr) [Google Scholar]

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