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Infection and Immunity, January 2006, p. 469-480, Vol. 74, No. 1
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.1.469-480.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Roles of Macrophages and Neutrophils in the Early Host Response to Bacillus anthracis Spores in a Mouse Model of Infection

Christopher K. Cote,1 Nico Van Rooijen,2 and Susan L. Welkos1*

Bacteriology Division, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, Frederick, Maryland 21702,1 Department of Cell Biology and Immunology, Free University, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands2

Received 15 July 2005/ Returned for modification 29 August 2005/ Accepted 13 October 2005

The development of new approaches to combat anthrax requires that the pathogenesis and host response to Bacillus anthracis spores be better understood. We investigated the roles that macrophages and neutrophils play in the progression of infection by B. anthracis in a mouse model. Mice were treated with a macrophage depletion agent (liposome-encapsulated clodronate) or with a neutrophil depletion agent (cyclophosphamide or the rat anti-mouse granulocyte monoclonal antibody RB6-8C5), and the animals were then infected intraperitoneally or by aerosol challenge with fully virulent, ungerminated B. anthracis strain Ames spores. The macrophage-depleted mice were significantly more susceptible to the ensuing infection than the saline-pretreated mice, whereas the differences observed between the neutropenic mice and the saline-pretreated controls were generally not significant. We also found that augmenting peritoneal neutrophil populations before spore challenge did not increase resistance of the mice to infection. In addition, the bacterial load in macrophage-depleted mice was significantly greater and appeared significantly sooner than that observed with the saline-pretreated mice. However, the bacterial load in the neutropenic mice was comparable to that of the saline-pretreated mice. These data suggest that, in our model, neutrophils play a relatively minor role in the early host response to spores, whereas macrophages play a more dominant role in early host defenses against infection by B. anthracis spores.

* Corresponding author. Mailing address: Bacteriology Division, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, Frederick, MD 21702. Phone: (301) 619-4930. Fax: (301) 619-2152. E-mail: susan.welkos{at}amedd.army.mil.

Editor: J. D. Clements

Infection and Immunity, January 2006, p. 469-480, Vol. 74, No. 1
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.1.469-480.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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