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Infection and Immunity, October 2006, p. 5679-5686, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.00837-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Protection against Lethal Challenge with Streptococcus pneumoniae Is Conferred by Aryl Hydrocarbon Receptor Activation but Is Not Associated with an Enhanced Inflammatory Response

Beth A. Vorderstrasse and B. Paige Lawrence^*

Department of Pharmaceutical Sciences, Washington State University, Pullman, Washington 99164-6534

Received 24 May 2006/ Returned for modification 7 July 2006/ Accepted 20 July 2006

Streptococcus pneumoniae is a common respiratory pathogen and a major cause of morbidity and mortality in humans, particularly in the elderly and young children. The pulmonary immune response to S. pneumoniae is initiated very rapidly, and, ideally, innate immune responses are able to contain bacterial colonization. In the studies presented here, we sought to determine whether activation of the aryl hydrocarbon receptor (AhR) would protect mice from an otherwise lethal infection with S. pneumoniae. The rationale for this hypothesis is that, although most AhR agonists are potent immunosuppressants, AhR activation enhances the inflammatory response to pathogenic and nonpathogenic stimuli. Specifically, neutrophil numbers and levels of inflammatory cytokines are often increased in mice treated with the potent AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). To test the hypothesis, vehicle control- or TCDD-treated mice were intranasally infected with S. pneumoniae. Mortality, pulmonary bacterial burden, cytokine/chemokine levels, and influx of immune cells to the lung were analyzed at various times postinfection. As predicted, survival was substantially improved in the mice treated with TCDD, and the pulmonary bacterial burden was decreased. Surprisingly, however, there was no evidence suggesting that protection resulted from an enhanced inflammatory response. In fact, neutrophil numbers and inflammatory chemokines and cytokines were all decreased in the TCDD-treated mice relative to vehicle control-treated mice. This suggests that the protective effect of AhR activation is not the result of altered immune function but instead may reflect a direct effect on the response of lung cells to infection.

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* Corresponding author. Present address: Dept. of Environmental Medicine, Box 850, University of Rochester School of Medicine, 575 Elmwood Avenue, Rochester, NY 14642. Phone: (585) 275-1974. Fax: (585) 276-0239. E-mail: paige_lawrence{at}urmc.rochester.edu.

Editor: J. N. Weiser

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Infection and Immunity, October 2006, p. 5679-5686, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.00837-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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