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. 1996 Dec;64(12):4933–4939. doi: 10.1128/iai.64.12.4933-4939.1996

Murine intranasal challenge model for the study of Campylobacter pathogenesis and immunity.

S Baqar 1, A L Bourgeois 1, L A Applebee 1, A S Mourad 1, M T Kleinosky 1, Z Mohran 1, J R Murphy 1
PMCID: PMC174471  PMID: 8945529

Abstract

Campylobacter jejuni infection of mice initiated by intranasal administration was investigated as a potential model for studies of pathogenesis and immunity. By using a standard challenge (5 x 10(9) CFU), C. jejuni 81-176 was more virulent for BALB/c (72% mortality) than for C3H/Hej (50%), CBA/CAJ (30%), or C58/J (0%). Intranasal challenge of BALB/c was used to compare the relative virulence of three reference strains; C.jejuni 81-176 was more virulent (killing 83% of challenged mice) than C. jejuni HC (0%) or C. coli VC-167 (0%). The course of intranasally initiated C. jejuni 81-176 infection in BALB/c was determined. C. jejuni was recovered from the lungs, intestinal tract, liver, and spleen at 4 h after challenge, the first interval evaluated. After this initial interval, three distinct patterns of infection were recognized: (i) a progressive decline in number of C. jejuni CFU (stomach, blood, lungs), (ii) decline followed by a second peak in the number of organisms recovered at 2 or 3 days postchallenge (intestine, liver, mesenteric lymph nodes), and (iii) persistence of approximately the same number of C.jejuni CFU during the course of the experiment (spleen). Intranasally induced infection initiated with a sublethal number of bacteria or intranasal immunization with killed Campylobacter preparations resulted in both the generation of Campylobacter antigen-specific immune responses and an acquired resistance to homologous rechallenge. The model was used to evaluate the relative virulence of nine low-in vitro-passage (no more than five passages) isolates of C. jejuni species from patients with diarrhea. The patient isolates were differentially virulent for mice; one killed all exposed mice, three were avirulent (no deaths) and the remainder showed an intermediate virulence, killing 17 to 33%. Mouse virulence of Campylobacter strains showed a trend toward isolates originating from individuals with watery diarrhea; however, no association was found between mouse virulence and other signs or symptoms. There were no observed relationships between mouse virulence and bacterial Lior serotype or Fla polymorphic group. Intranasal challenge of BALB/c with C. jejuni is a useful model for the study of infection and vaccination-acquired immunity to this agent.

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Selected References

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  1. Abimiku A. G., Dolby J. M. The mechanism of protection of infant mice from intestinal colonisation with Campylobacter jejuni. J Med Microbiol. 1987 Jun;23(4):339–344. doi: 10.1099/00222615-23-4-339. [DOI] [PubMed] [Google Scholar]
  2. Aguero-Rosenfeld M. E., Yang X. H., Nachamkin I. Infection of adult Syrian hamsters with flagellar variants of Campylobacter jejuni. Infect Immun. 1990 Jul;58(7):2214–2219. doi: 10.1128/iai.58.7.2214-2219.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Al-Mashat R. R., Taylor D. J. Production of diarrhoea and dysentery in experimental calves by feeding pure cultures of Campylobacter fetus subspecies jejuni. Vet Rec. 1980 Nov 15;107(20):459–464. doi: 10.1136/vr.107.20.459. [DOI] [PubMed] [Google Scholar]
  4. Alm R. A., Guerry P., Trust T. J. Distribution and polymorphism of the flagellin genes from isolates of Campylobacter coli and Campylobacter jejuni. J Bacteriol. 1993 May;175(10):3051–3057. doi: 10.1128/jb.175.10.3051-3057.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Babakhani F. K., Bradley G. A., Joens L. A. Newborn piglet model for campylobacteriosis. Infect Immun. 1993 Aug;61(8):3466–3475. doi: 10.1128/iai.61.8.3466-3475.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Baqar S., Applebee L. A., Bourgeois A. L. Immunogenicity and protective efficacy of a prototype Campylobacter killed whole-cell vaccine in mice. Infect Immun. 1995 Sep;63(9):3731–3735. doi: 10.1128/iai.63.9.3731-3735.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Baqar S., Bourgeois A. L., Schultheiss P. J., Walker R. I., Rollins D. M., Haberberger R. L., Pavlovskis O. R. Safety and immunogenicity of a prototype oral whole-cell killed Campylobacter vaccine administered with a mucosal adjuvant in non-human primates. Vaccine. 1995 Jan;13(1):22–28. doi: 10.1016/0264-410x(95)80006-y. [DOI] [PubMed] [Google Scholar]
  8. Baqar S., Pacheco N. D., Rollwagen F. M. Modulation of mucosal immunity against Campylobacter jejuni by orally administered cytokines. Antimicrob Agents Chemother. 1993 Dec;37(12):2688–2692. doi: 10.1128/aac.37.12.2688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bell J. A., Manning D. D. A domestic ferret model of immunity to Campylobacter jejuni-induced enteric disease. Infect Immun. 1990 Jun;58(6):1848–1852. doi: 10.1128/iai.58.6.1848-1852.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Berndtson E., Danielsson-Tham M. L., Engvall A. Experimental colonization of mice with Campylobacter jejuni. Vet Microbiol. 1994 Jul;41(1-2):183–188. doi: 10.1016/0378-1135(94)90147-3. [DOI] [PubMed] [Google Scholar]
  11. Black R. E., Levine M. M., Clements M. L., Hughes T. P., Blaser M. J. Experimental Campylobacter jejuni infection in humans. J Infect Dis. 1988 Mar;157(3):472–479. doi: 10.1093/infdis/157.3.472. [DOI] [PubMed] [Google Scholar]
  12. Blaser M. J., Duncan D. J., Warren G. H., Wang W. L. Experimental Campylobacter jejuni infection of adult mice. Infect Immun. 1983 Feb;39(2):908–916. doi: 10.1128/iai.39.2.908-916.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Blaser M. J., Taylor D. N., Feldman R. A. Epidemiology of Campylobacter jejuni infections. Epidemiol Rev. 1983;5:157–176. doi: 10.1093/oxfordjournals.epirev.a036256. [DOI] [PubMed] [Google Scholar]
  14. Burr D. H., Caldwell M. B., Bourgeois A. L., Morgan H. R., Wistar R., Jr, Walker R. I. Mucosal and systemic immunity to Campylobacter jejuni in rabbits after gastric inoculation. Infect Immun. 1988 Jan;56(1):99–105. doi: 10.1128/iai.56.1.99-105.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Caldwell M. B., Walker R. I., Stewart S. D., Rogers J. E. Simple adult rabbit model for Campylobacter jejuni enteritis. Infect Immun. 1983 Dec;42(3):1176–1182. doi: 10.1128/iai.42.3.1176-1182.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Cawthraw S., Ayling R., Nuijten P., Wassenaar T., Newell D. G. Isotype, specificity, and kinetics of systemic and mucosal antibodies to Campylobacter jejuni antigens, including flagellin, during experimental oral infections of chickens. Avian Dis. 1994 Apr-Jun;38(2):341–349. [PubMed] [Google Scholar]
  17. Fitzgeorge R. B., Baskerville A., Lander K. P. Experimental infection of Rhesus monkeys with a human strain of Campylobacter jejuni. J Hyg (Lond) 1981 Jun;86(3):343–351. doi: 10.1017/s0022172400069096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Fox J. G., Ackerman J. I., Taylor N., Claps M., Murphy J. C. Campylobacter jejuni infection in the ferret: an animal model of human campylobacteriosis. Am J Vet Res. 1987 Jan;48(1):85–90. [PubMed] [Google Scholar]
  19. Guerrant R. L., Lahita R. G., Winn W. C., Jr, Roberts R. B. Campylobacteriosis in man: pathogenic mechanisms and review of 91 bloodstream infections. Am J Med. 1978 Oct;65(4):584–592. doi: 10.1016/0002-9343(78)90845-8. [DOI] [PubMed] [Google Scholar]
  20. Harris J. C., Dupont H. L., Hornick R. B. Fecal leukocytes in diarrheal illness. Ann Intern Med. 1972 May;76(5):697–703. doi: 10.7326/0003-4819-76-5-697. [DOI] [PubMed] [Google Scholar]
  21. Humphrey C. D., Montag D. M., Pittman F. E. Experimental infection of hamsters with Campylobacter jejuni. J Infect Dis. 1985 Mar;151(3):485–493. doi: 10.1093/infdis/151.3.485. [DOI] [PubMed] [Google Scholar]
  22. Hörnqvist E., Goldschmidt T. J., Holmdahl R., Lycke N. Host defense against cholera toxin is strongly CD4+ T cell dependent. Infect Immun. 1991 Oct;59(10):3630–3638. doi: 10.1128/iai.59.10.3630-3638.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lior H. New, extended biotyping scheme for Campylobacter jejuni, Campylobacter coli, and "Campylobacter laridis". J Clin Microbiol. 1984 Oct;20(4):636–640. doi: 10.1128/jcm.20.4.636-640.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Logan S. M., Trust T. J. Outer membrane characteristics of Campylobacter jejuni. Infect Immun. 1982 Dec;38(3):898–906. doi: 10.1128/iai.38.3.898-906.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mallett C. P., Hale T. L., Kaminski R. W., Larsen T., Orr N., Cohen D., Lowell G. H. Intransal or intragastric immunization with proteosome-Shigella lipopolysaccharide vaccines protects against lethal pneumonia in a murine model of Shigella infection. Infect Immun. 1995 Jun;63(6):2382–2386. doi: 10.1128/iai.63.6.2382-2386.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mallett C. P., VanDeVerg L., Collins H. H., Hale T. L. Evaluation of Shigella vaccine safety and efficacy in an intranasally challenged mouse model. Vaccine. 1993;11(2):190–196. doi: 10.1016/0264-410x(93)90016-q. [DOI] [PubMed] [Google Scholar]
  27. Mohran Z. S., Guerry P., Lior H., Murphy J. R., el-Gendy A. M., Mikhail M. M., Oyofo B. A. Restriction fragment length polymorphism of flagellin genes of Campylobacter jejuni and/or C. coli isolates from Egypt. J Clin Microbiol. 1996 May;34(5):1216–1219. doi: 10.1128/jcm.34.5.1216-1219.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Munoz C., Baqar S., van de Verg L., Thupari J., Goldblum S., Olson J. G., Taylor D. N., Heresi G. P., Murphy J. R. Characteristics of Shigella sonnei infection of volunteers: signs, symptoms, immune responses, changes in selected cytokines and acute-phase substances. Am J Trop Med Hyg. 1995 Jul;53(1):47–54. [PubMed] [Google Scholar]
  29. Mäki M., Mäki R., Vesikari T. Faecal leucocytes in campylobacter-associated diarrhoea in infants. Acta Paediatr Scand. 1979 Mar;68(2):271–272. doi: 10.1111/j.1651-2227.1979.tb05000.x. [DOI] [PubMed] [Google Scholar]
  30. Prescott J. F., Barker I. K., Manninen K. I., Miniats O. P. Campylobacter jejuni colitis in gnotobiotic dogs. Can J Comp Med. 1981 Oct;45(4):377–383. [PMC free article] [PubMed] [Google Scholar]
  31. Rollwagen F. M., Pacheco N. D., Clements J. D., Pavlovskis O., Rollins D. M., Walker R. I. Killed Campylobacter elicits immune response and protection when administered with an oral adjuvant. Vaccine. 1993 Oct;11(13):1316–1320. doi: 10.1016/0264-410x(93)90101-3. [DOI] [PubMed] [Google Scholar]
  32. Russell R. G., O'Donnoghue M., Blake D. C., Jr, Zulty J., DeTolla L. J. Early colonic damage and invasion of Campylobacter jejuni in experimentally challenged infant Macaca mulatta. J Infect Dis. 1993 Jul;168(1):210–215. doi: 10.1093/infdis/168.1.210. [DOI] [PubMed] [Google Scholar]
  33. Skirrow M. B., Jones D. M., Sutcliffe E., Benjamin J. Campylobacter bacteraemia in England and Wales, 1981-91. Epidemiol Infect. 1993 Jun;110(3):567–573. doi: 10.1017/s0950268800050986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Stanfield J. T., McCardell B. A., Madden J. M. Campylobacter diarrhea in an adult mouse model. Microb Pathog. 1987 Sep;3(3):155–165. doi: 10.1016/0882-4010(87)90092-1. [DOI] [PubMed] [Google Scholar]
  35. Taylor D. E., Bryner J. H. Plasmid content and pathogenicity of Campylobacter jejuni and Campylobacter coli strains in the pregnant guinea pig model. Am J Vet Res. 1984 Oct;45(10):2201–2202. [PubMed] [Google Scholar]
  36. van de Verg L. L., Mallett C. P., Collins H. H., Larsen T., Hammack C., Hale T. L. Antibody and cytokine responses in a mouse pulmonary model of Shigella flexneri serotype 2a infection. Infect Immun. 1995 May;63(5):1947–1954. doi: 10.1128/iai.63.5.1947-1954.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]

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