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Infection and Immunity, April 2009, p. 1664-1678, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.01208-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Antimicrobial Effects of Interferon-Inducible CXC Chemokines against Bacillus anthracis Spores and Bacilli{triangledown}

Matthew A. Crawford,1 Yinghua Zhu,1 Candace S. Green,1 Marie D. Burdick,2 Patrick Sanz,3 Farhang Alem,3 Alison D. O'Brien,3 Borna Mehrad,2 Robert M. Strieter,2 and Molly A. Hughes1*

Department of Medicine, Division of Infectious Diseases, University of Virginia Health Sciences System, Charlottesville, Virginia,1 Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Virginia Health Sciences System, Charlottesville, Virginia,2 Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland3

Received 29 September 2008/ Returned for modification 10 November 2008/ Accepted 21 January 2009

Based on previous studies showing that host chemokines exert antimicrobial activities against bacteria, we sought to determine whether the interferon-inducible Glu-Leu-Arg-negative CXC chemokines CXCL9, CXCL10, and CXCL11 exhibit antimicrobial activities against Bacillus anthracis. In vitro analysis demonstrated that all three CXC chemokines exerted direct antimicrobial effects against B. anthracis spores and bacilli including marked reductions in spore and bacillus viability as determined using a fluorometric assay of bacterial viability and CFU determinations. Electron microscopy studies revealed that CXCL10-treated spores failed to undergo germination as judged by an absence of cytological changes in spore structure that occur during the process of germination. Immunogold labeling of CXCL10-treated spores demonstrated that the chemokine was located internal to the exosporium in association primarily with the spore coat and its interface with the cortex. To begin examining the potential biological relevance of chemokine-mediated antimicrobial activity, we used a murine model of inhalational anthrax. Upon spore challenge, the lungs of C57BL/6 mice (resistant to inhalational B. anthracis infection) had significantly higher levels of CXCL9, CXCL10, and CXCL11 than did the lungs of A/J mice (highly susceptible to infection). Increased CXC chemokine levels were associated with significantly reduced levels of spore germination within the lungs as determined by in vivo imaging. Taken together, our data demonstrate a novel antimicrobial role for host chemokines against B. anthracis that provides unique insight into host defense against inhalational anthrax; these data also support the notion for an innovative approach in treating B. anthracis infection as well as infections caused by other spore-forming organisms.

* Corresponding author. Mailing address: Department of Medicine, Division of Infectious Diseases, University of Virginia Health Sciences System, P.O. Box 800513, Charlottesville, VA 22908. Phone: (434) 924-5216. Fax: (434) 982-3830. E-mail: mah3x{at}virginia.edu

{triangledown} Published ahead of print on 29 January 2009.

Editor: S. R. Blanke

Infection and Immunity, April 2009, p. 1664-1678, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.01208-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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