Heterologous infection causes pneumonia and impairs alveolar macrophage function in mice
M. R. Stampfli, C. M. T. Bauer, G. J. Gaschler, K. M. Fraser, S. Kianpour, C. C. J. Zavitz (Hamilton, ON, Canada)
Source: Annual Congress 2008 - Mechanisms of respiratory infections: interaction between the pathogen and the host
Disease area: Respiratory infections
Abstract Experimental studies of infectious disease typically examine the impact of a single agent on a specific pathogen free animal. Although necessary to our understanding of disease, such studies do not fully recapitulate the case seen in the clinic, where patients frequently present with multiple simultaneous infections, and at very least present with a history of other infections. We have established a model of heterologous pulmonary infection in which mice are infected with influenza virus, and then 5 days later are given a sub-clinical dose of Bordetella (B.) parapertussis . Mice infected with both pathogens suffered exacerbated and prolonged weight loss, and increased duration of symptoms. These impairments were associated with dramatically increased bacterial burden, and severe pulmonary neutrophillia, both in the lung and in the broncho-alveolar lavage, with concomitantly elevated neutrophil myeloperoxidase activity. In contrast to this robust neutrophil activity, alveolar macrophage responses were attenuated; alveolar macrophages taken from influenza-infected animals produced significantly less TNFα, a crucial, early mediator of Bordetella clearance. We thus propose a model in which influenza infection alters alveolar macrophage function, in a way which makes the lungs a permissive environment for B. parapertussis . Collectively, these results indicate that influenza infection can substantially impair the antibacterial response against B. parapertussis , and underscore the need to develop complex models of disease, which can better recapitulate a human host with a history of current or prior infection. Funded by the Canadian Institutes of Health Research.
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M. R. Stampfli, C. M. T. Bauer, G. J. Gaschler, K. M. Fraser, S. Kianpour, C. C. J. Zavitz (Hamilton, ON, Canada). Heterologous infection causes pneumonia and impairs alveolar macrophage function in mice. Eur Respir J 2008; 32: Suppl. 52, 2296
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