Abstract
Studies with animal models have demonstrated that viral respiratory tract infections suppress bacterial clearance processes in the lung and that this alteration in host defenses appears to explain the excessive mortality from bacterial pneumonia during influenza epidemics. However, since the pathogenesis of postinfluenza pneumonia and other pneumonias probably involves the aspiration of normal nasopharyngeal flora, injury to major airways associated with influenza infections could also contribute to the development of bacterial pneumonia by increasing bacterial deposition in the peripheral lung. We investigated this possibility by evaluating tracheal clearance processes and spontaneous changes in the tracheal flora in a murine model for acute influenza. During fine-particle aerosol exposures to Staphylococcus aureus, influenza-infected mice retained the same number of bacteria on their proximal tracheal surfaces as did control mice, and the relative adherence of the staphylococci to the trachea was similar in both groups of mice. However, the clearance of viable staphylococci from the trachea was significantly delayed in influenza-infected mice. Control and influenza-infected mice were also evaluated for changes in their normal tracheal flora. Mice with established influenza infections had more frequent spontaneous colonization with gram-negative bacteria, more bacterial isolates per animal, and higher bacterial concentrations in tracheal homogenates than control mice. These changes in tracheal flora were most pronounced on day 7 after virus inoculation and persisted after virus titers were undetectable, but eventually resolved by day 14 after virus infection. Tetracycline therapy started 2 days after virus inoculation prevented the increased colonization. This impaired clearance function and increased spontaneous colonization were associated with morphological evidence of mucosal regeneration. We conclude that spontaneous changes in tracheal flora occur during influenza infections, that these changes reflect, in part, impaired clearance functions, and that such changes could contribute to the development of pneumonia regardless of the clearance capacity of the lung parenchyma.
Full text
PDF






Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Blackwelder W. C., Alling D. W., Stuart-Harris C. H. Association of excess mortality from chronic nonspecific lung disease with epidemics of influenza. Comparison of experience in the United States and in England and Wales, 1968 to 1976. Am Rev Respir Dis. 1982 May;125(5):511–516. doi: 10.1164/arrd.1982.125.5.511. [DOI] [PubMed] [Google Scholar]
- Davison V. E., Sanford B. A. Adherence of staphylococcus aureus to influenza A virus-infected Madin-Darby canine kidney cell cultures. Infect Immun. 1981 Apr;32(1):118–126. doi: 10.1128/iai.32.1.118-126.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ellis D. A., Anderson I. M., Stewart S. M., Calder J., Crofton J. W. Exacerbations of chronic bronchitis: exogenous or endogenous infection? Br J Dis Chest. 1978 Apr;72(2):115–121. doi: 10.1016/0007-0971(78)90020-7. [DOI] [PubMed] [Google Scholar]
- Gump D. W., Phillips C. A., Forsyth B. R., McIntosh K., Lamborn K. R., Stouch W. H. Role of infection in chronic bronchitis. Am Rev Respir Dis. 1976 Apr;113(4):465–474. doi: 10.1164/arrd.1976.113.4.465. [DOI] [PubMed] [Google Scholar]
- Gwaltney J. M., Jr, Sande M. A., Austrian R., Hendley J. O. Spread of Streptococcus pneumoniae in families. II. Relation of transfer of S. pneumoniae to incidence of colds and serum antibody. J Infect Dis. 1975 Jul;132(1):62–68. doi: 10.1093/infdis/132.1.62. [DOI] [PubMed] [Google Scholar]
- Jakab G. J., Dick E. C. Synergistic effect in viral-bacterial infection: combined infection of the murine respiratory tract with Sendai virus and Pasteurella pneumotropica. Infect Immun. 1973 Nov;8(5):762–768. doi: 10.1128/iai.8.5.762-768.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jakab G. J., Green G. M. Defect in intracellular killing of Staphylococcus aureus within alveolar macrophages in Sendai virus-infected murine lungs. J Clin Invest. 1976 Jun;57(6):1533–1539. doi: 10.1172/JCI108423. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jakab G. J., Green G. M. The effect of Sendai virus infection on bactericidal and transport mechanisms of the murine lung. J Clin Invest. 1972 Aug;51(8):1989–1998. doi: 10.1172/JCI107005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nugent K. M., Pesanti E. L. Effect of influenza infection on the phagocytic and bactericidal activities of pulmonary macrophages. Infect Immun. 1979 Nov;26(2):651–657. doi: 10.1128/iai.26.2.651-657.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nugent K. M., Pesanti E. L. Nonphagocytic clearance of Staphylococcus aureus from murine lungs. Infect Immun. 1982 Jun;36(3):1185–1191. doi: 10.1128/iai.36.3.1185-1191.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nugent K. M., Pesanti E. L. Staphylococcal clearance and pulmonary macrophage function during influenza infection. Infect Immun. 1982 Dec;38(3):1256–1262. doi: 10.1128/iai.38.3.1256-1262.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Onofrio J. M., Toews G. B., Lipscomb M. F., Pierce A. K. Granulocyte-alveolar-macrophage interaction in the pulmonary clearance of Staphylococcus aureus. Am Rev Respir Dis. 1983 Mar;127(3):335–341. doi: 10.1164/arrd.1983.127.3.335. [DOI] [PubMed] [Google Scholar]
- Ramphal R., Fischlschweiger W., Shands J. W., Jr, Small P. A., Jr Murine influenzal tracheitis: a model for the study of influenza and tracheal epithelial repair. Am Rev Respir Dis. 1979 Dec;120(6):1313–1324. doi: 10.1164/arrd.1979.120.6.1313. [DOI] [PubMed] [Google Scholar]
- Ramphal R., Small P. M., Shands J. W., Jr, Fischlschweiger W., Small P. A., Jr Adherence of Pseudomonas aeruginosa to tracheal cells injured by influenza infection or by endotracheal intubation. Infect Immun. 1980 Feb;27(2):614–619. doi: 10.1128/iai.27.2.614-619.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SELLERS T. F., Jr, SCHULMAN J., BOUVIER C., McCUNE R., KILBOURNE E. D. The influence of influenza virus infection on exogenous staphylococcal and endogenous murine bacterial infection of the bronchopulmonary tissues of mice. J Exp Med. 1961 Aug 1;114:237–256. doi: 10.1084/jem.114.2.237. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Selinger D. S., Reed W. P., McLaren L. C. Model for studying bacterial adherence to epithelial cells infected with viruses. Infect Immun. 1981 May;32(2):941–944. doi: 10.1128/iai.32.2.941-944.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith C. B., Golden C. A., Kanner R. E., Renzetti A. D., Jr Association of viral and Mycoplasma pneumoniae infections with acute respiratory illness in patients with chronic obstructive pulmonary diseases. Am Rev Respir Dis. 1980 Feb;121(2):225–232. doi: 10.1164/arrd.1980.121.2.225. [DOI] [PubMed] [Google Scholar]
- Sweet C., Macartney J. C., Bird R. A., Cavanagh D., Collie M. H., Husseini R. H., Smith H. Differential distribution of virus and histological damage in the lower respiratory tract of ferrets infected with influenza viruses of differing virulence. J Gen Virol. 1981 May;54(Pt 1):103–114. doi: 10.1099/0022-1317-54-1-103. [DOI] [PubMed] [Google Scholar]
- Yealland S. J., Heath R. B. The significance of secondary gram-negative coliform infection of the lungs of mice with influenzal pneumonitis. Br J Exp Pathol. 1978 Feb;59(1):48–51. [PMC free article] [PubMed] [Google Scholar]
- Young L. S., LaForce F. M., Head J. J., Feeley J. C., Bennett J. V. A simultaneous outbreak of meningococcal and influenza infections. N Engl J Med. 1972 Jul 6;287(1):5–9. doi: 10.1056/NEJM197207062870102. [DOI] [PubMed] [Google Scholar]

