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Infection and Immunity, April 2007, p. 1757-1764, Vol. 75, No. 4
0019-9567/07/$08.00+0     doi:10.1128/IAI.01712-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Murine Innate Immune Response to Virulent Toxigenic and Nontoxigenic Bacillus anthracis Strains{triangledown}

Melissa Drysdale,1 Gwyneth Olson,2 Theresa M. Koehler,3 Mary F. Lipscomb,4 and C. Rick Lyons1*

Department of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, New Mexico 87131,1 Department of Pathology, University of New Mexico Health Science Center, Albuquerque, New Mexico 87131,2 Department of Microbiology and Molecular Genetics, The University of Texas Houston Health Science Center, Houston, Texas 77030,3 Department of Pathology, University of New Mexico Health Science Center, Albuquerque, New Mexico 871314

Received 25 October 2006/ Returned for modification 17 November 2006/ Accepted 11 January 2007

Effective treatment of anthrax is hampered by our limited understanding of the pathophysiology of Bacillus anthracis infection. We used a genetically complete (pXO1+ pXO2+) virulent B. anthracis strain and four isogenic toxin-null mutants to determine the effects of the anthrax edema toxin (ET; edema factor [EF] plus protective antigen [PA]) and lethal toxin (LT; lethal factor [LF] plus PA) on the host innate response during systemic infection. Using the spleen as an indicator for host response, we found that intravenous inoculation of LT-deficient mutants into C57BL/6 mice significantly increased production of several cytokines over that observed after infection with the parent strain or an EF-deficient mutant. Bacteria producing one or both of the toxins were capable of inducing significant apoptosis of cells present in spleens, whereas apoptosis was greatly reduced in mice infected with nontoxigenic mutants. Mice infected with toxin-producing strains also showed increased splenic neutrophil recruitment compared to mice infected with nontoxigenic strains and neutrophil depletion prior to infection with toxin-producing strains, leading to decreased levels of apoptosis. Together, these studies indicate that anthrax LT suppresses cytokine secretion during infection, but both EF and LF play roles in inducing neutrophil recruitment and enhancing apoptosis. Interestingly, in the absence of LF the effect of EF-induced cell recruitment is further enhanced, perhaps because LF so effectively suppresses the secretion of chemokines.

* Corresponding author. Mailing address: Department of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, NM 87131. Phone: (505) 272-4150. Fax: (505) 272-4160. E-mail: clyons{at}salud.unm.edu.

{triangledown} Published ahead of print on 22 January 2007.

Editor: R. P. Morrison

Infection and Immunity, April 2007, p. 1757-1764, Vol. 75, No. 4
0019-9567/07/$08.00+0     doi:10.1128/IAI.01712-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Loving, C. L., Khurana, T., Osorio, M., Lee, G. M., Kelly, V. K., Stibitz, S., Merkel, T. J. (2009). Role of Anthrax Toxins in Dissemination, Disease Progression, and Induction of Protective Adaptive Immunity in the Mouse Aerosol Challenge Model. Infect. Immun. 77: 255-265 [Abstract] [Full Text]  
  • Chand, H. S., Drysdale, M., Lovchik, J., Koehler, T. M., Lipscomb, M. F., Lyons, C. R. (2009). Discriminating Virulence Mechanisms among Bacillus anthracis Strains by Using a Murine Subcutaneous Infection Model. Infect. Immun. 77: 429-435 [Abstract] [Full Text]  


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