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Infection and Immunity, January 2009, p. 532-538, Vol. 77, No. 1
0019-9567/09/$08.00+0     doi:10.1128/IAI.01009-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Macrophage Uptake, Intracellular Localization, and Degradation of Poly-{gamma}-D-Glutamic Acid, the Capsular Antigen of Bacillus anthracis {triangledown}

Marjorie D. Sutherland and Thomas R. Kozel*

Department of Microbiology and Immunology and Cell and Molecular Biology Program, University of Nevada School of Medicine, Reno, Nevada 89557

Received 12 August 2008/ Returned for modification 15 September 2008/ Accepted 31 October 2008

Bacillus anthracis is surrounded by a capsular polypeptide composed of poly-{gamma}-D-glutamic acid (PGA). This antiphagocytic capsule is an essential virulence factor and is shed into body fluids during a murine model of pulmonary anthrax. Our previous studies of a murine model for antigen clearance showed that purified PGA accumulates in the liver and spleen, most notably in splenic macrophages and the Kupffer cells and sinusoidal endothelial cells of the liver. Although the tissue and cellular depots have been identified, there is little known about the uptake and intracellular fate of PGA. As a consequence, we examined the cellular uptake and organelle localization of PGA in the murine macrophage-like cell line J774.2. We found that PGA binds to and is internalized by J774.2 cells and accumulates in CD71 transferrin receptor-positive endosomes. The receptor-mediated endocytosis inhibitors amantadine and phenylarsine oxide inhibited the binding and uptake of PGA in these cells. Cytochalasin D and vinblastine, actin and microtubule inhibitors, respectively, failed to completely inhibit binding and uptake. Finally, we found that PGA is degraded in J774.2 cells starting 4 h after uptake, with continued degradation occurring for at least 24 h. This degradation of PGA may explain the rapid clearance of PGA that is observed in vivo compared to the slow clearance noted with capsular polysaccharides.

* Corresponding author. Mailing address: Department of Microbiology and Immunology/320, University of Nevada School of Medicine, Reno, NV 89557. Phone: (775) 784-4124. Fax: (775) 327-2332. E-mail: tkozel{at}medicine.nevada.edu

{triangledown} Published ahead of print on 10 November 2008.

Editor: A. Casadevall

Infection and Immunity, January 2009, p. 532-538, Vol. 77, No. 1
0019-9567/09/$08.00+0     doi:10.1128/IAI.01009-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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