Abstract
Using a mouse model of Bordetella pertussis infection, we have analyzed the role of gamma interferon (IFN-gamma) in bacterial clearance from the respiratory tract. Adult BALB/c mice began to clear a respiratory infection within 3 weeks postinfection, with complete resolution of infection 6 to 8 weeks postinfection. In contrast, neither adult SCID mice (which lack mature B and T lymphocytes) nor adult nude mice (which lack mature T lymphocytes) controlled B. pertussis infection, and both strains died within 3 to 5 weeks postinfection. Short-term T-cell lines generated from the draining lymph nodes of the lungs of infected BALB/c mice were found to be CD4+ and produced IFN-gamma but no detectable interleukin-4. Analyses of IFN-gamma mRNA induction in the lungs of mice following B. pertussis infection showed that in both BALB/c and C57BL/6 mice, IFN-gamma mRNA levels increased sharply by 1 week postinfection and then subsequently declined. Further exploration of a potential role for IFN-gamma demonstrated that infection of adult BALB/c mice depleted of IFN-gamma in vivo with anti-IFN-gamma monoclonal antibodies resulted in greater numbers of bacteria recovered from the lungs than in infected, control BALB/c mice, although IFN-gamma-depleted mice could subsequently clear the infection. Infection of mice which have a disrupted IFN-gamma gene resulted in bacterial clearance with a time course similar to those seen with IFN-gamma-depleted mice. These results indicate that IFN-gamma plays a role in controlling B. pertussis infection.
Full Text
The Full Text of this article is available as a PDF (164.2 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Berkower I., Kawamura H., Matis L. A., Berzofsky J. A. T cell clones to two major T cell epitopes of myoglobin: effect of I-A/I-E restriction on epitope dominance. J Immunol. 1985 Oct;135(4):2628–2634. [PubMed] [Google Scholar]
- Celada A., Klemsz M. J., Maki R. A. Interferon-gamma activates multiple pathways to regulate the expression of the genes for major histocompatibility class II I-A beta, tumor necrosis factor and complement component C3 in mouse macrophages. Eur J Immunol. 1989 Jun;19(6):1103–1109. doi: 10.1002/eji.1830190621. [DOI] [PubMed] [Google Scholar]
- Dalton D. K., Pitts-Meek S., Keshav S., Figari I. S., Bradley A., Stewart T. A. Multiple defects of immune cell function in mice with disrupted interferon-gamma genes. Science. 1993 Mar 19;259(5102):1739–1742. doi: 10.1126/science.8456300. [DOI] [PubMed] [Google Scholar]
- De Magistris M. T., Romano M., Nuti S., Rappuoli R., Tagliabue A. Dissecting human T cell responses against Bordetella species. J Exp Med. 1988 Oct 1;168(4):1351–1362. doi: 10.1084/jem.168.4.1351. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Halperin S. A., Issekutz T. B., Kasina A. Modulation of Bordetella pertussis infection with monoclonal antibodies to pertussis toxin. J Infect Dis. 1991 Feb;163(2):355–361. doi: 10.1093/infdis/163.2.355. [DOI] [PubMed] [Google Scholar]
- Khelef N., Bachelet C. M., Vargaftig B. B., Guiso N. Characterization of murine lung inflammation after infection with parental Bordetella pertussis and mutants deficient in adhesins or toxins. Infect Immun. 1994 Jul;62(7):2893–2900. doi: 10.1128/iai.62.7.2893-2900.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mills K. H., Barnard A., Watkins J., Redhead K. Cell-mediated immunity to Bordetella pertussis: role of Th1 cells in bacterial clearance in a murine respiratory infection model. Infect Immun. 1993 Feb;61(2):399–410. doi: 10.1128/iai.61.2.399-410.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mountzouros K. T., Kimura A., Cowell J. L. A bactericidal monoclonal antibody specific for the lipooligosaccharide of Bordetella pertussis reduces colonization of the respiratory tract of mice after aerosol infection with B. pertussis. Infect Immun. 1992 Dec;60(12):5316–5318. doi: 10.1128/iai.60.12.5316-5318.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Peppoloni S., Nencioni L., Di Tommaso A., Tagliabue A., Parronchi P., Romagnani S., Rappuoli R., De Magistris M. T. Lymphokine secretion and cytotoxic activity of human CD4+ T-cell clones against Bordetella pertussis. Infect Immun. 1991 Oct;59(10):3768–3773. doi: 10.1128/iai.59.10.3768-3773.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Redhead K., Watkins J., Barnard A., Mills K. H. Effective immunization against Bordetella pertussis respiratory infection in mice is dependent on induction of cell-mediated immunity. Infect Immun. 1993 Aug;61(8):3190–3198. doi: 10.1128/iai.61.8.3190-3198.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sadick M. D., Heinzel F. P., Holaday B. J., Pu R. T., Dawkins R. S., Locksley R. M. Cure of murine leishmaniasis with anti-interleukin 4 monoclonal antibody. Evidence for a T cell-dependent, interferon gamma-independent mechanism. J Exp Med. 1990 Jan 1;171(1):115–127. doi: 10.1084/jem.171.1.115. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sato H., Ito A., Chiba J., Sato Y. Monoclonal antibody against pertussis toxin: effect on toxin activity and pertussis infections. Infect Immun. 1984 Nov;46(2):422–428. doi: 10.1128/iai.46.2.422-428.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schreiber R. D., Celada A., Buchmeier N. The role of interferon-gamma in the induction of activated macrophages. Ann Inst Pasteur Immunol. 1986 Mar-Apr;137C(2):203–206. doi: 10.1016/s0771-050x(86)80028-6. [DOI] [PubMed] [Google Scholar]
- Shahin R. D., Brennan M. J., Li Z. M., Meade B. D., Manclark C. R. Characterization of the protective capacity and immunogenicity of the 69-kD outer membrane protein of Bordetella pertussis. J Exp Med. 1990 Jan 1;171(1):63–73. doi: 10.1084/jem.171.1.63. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shahin R. D., Cowell J. L. Mouse respiratory infection models for pertussis. Methods Enzymol. 1994;235:47–58. doi: 10.1016/0076-6879(94)35130-9. [DOI] [PubMed] [Google Scholar]
- Shahin R. D., Hamel J., Leef M. F., Brodeur B. R. Analysis of protective and nonprotective monoclonal antibodies specific for Bordetella pertussis lipooligosaccharide. Infect Immun. 1994 Feb;62(2):722–725. doi: 10.1128/iai.62.2.722-725.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Svetić A., Finkelman F. D., Jian Y. C., Dieffenbach C. W., Scott D. E., McCarthy K. F., Steinberg A. D., Gause W. C. Cytokine gene expression after in vivo primary immunization with goat antibody to mouse IgD antibody. J Immunol. 1991 Oct 1;147(7):2391–2397. [PubMed] [Google Scholar]