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Infection and Immunity, June 2007, p. 2689-2698, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.01875-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Murine Aerosol Challenge Model of Anthrax{triangledown}

Crystal L. Loving,1 Mary Kennett,2 Gloria M. Lee,1 Vanessa K. Grippe,1 and Tod J. Merkel1*

Laboratory of Respiratory and Special Pathogens, Center for Biologics Evaluation and Research, Food and Drug Administration, 8800 Rockville Pike, Bethesda, Maryland 20892,1 Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, State College, Pennysylvania2

Received 28 November 2006/ Returned for modification 14 February 2007/ Accepted 28 February 2007

The availability of relevant and useful animal models is critical for progress in the development of effective vaccines and therapeutics. The infection of rabbits and non-human primates with fully virulent Bacillus anthracis spores provides two excellent models of anthrax disease. However, the high cost of procuring and housing these animals and the specialized facilities required to deliver fully virulent spores limit their practical use in early stages of product development. Conversely, the small size and low cost associated with using mice makes this animal model more practical for conducting experiments in which large numbers of animals are required. In addition, the availability of knockout strains and well-characterized immunological reagents makes it possible to perform studies in mice that cannot be performed easily in other species. Although we, along with others, have used the mouse aerosol challenge model to examine the outcome of B. anthracis infection, a detailed characterization of the disease is lacking. The current study utilizes a murine aerosol challenge model to investigate disease progression, innate cytokine responses, and histological changes during the course of anthrax after challenge with aerosolized spores. Our results show that anthrax disease progression in a complement-deficient mouse after challenge with aerosolized Sterne spores is similar to that described for other species, including rabbits and non-human primates, challenged with fully virulent B. anthracis. Thus, the murine aerosol challenge model is both useful and relevant and provides a means to further investigate the host response and mechanisms of B. anthracis pathogenesis.

* Corresponding author. Mailing address: Laboratory of Respiratory and Special Pathogens, DBPAP/CBER/FDA, Building 29, Room 418, 29 Lincoln Drive, Bethesda, MD 20892. Phone: (301) 496-5564. Fax: (301) 402-2776. E-mail: merkel{at}cber.fda.gov

{triangledown} Published ahead of print on 12 March 2007.

Editor: V. J. DiRita

Infection and Immunity, June 2007, p. 2689-2698, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.01875-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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