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Infection and Immunity, November 2004, p. 6382-6389, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6382-6389.2004

Cytokine Response to Infection with Bacillus anthracis Spores

Alison K. Pickering,1,{dagger} Manuel Osorio,2 Gloria M. Lee,1 Vanessa K. Grippe,1 Mechelle Bray,2 and Tod J. Merkel1*

Laboratory of Respiratory and Special Pathogens,1 Laboratory of Enteric and Sexually Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland2

Received 10 June 2004/ Returned for modification 15 July 2004/ Accepted 1 August 2004

Bacillus anthracis, the etiological agent of anthrax, is a gram-positive, spore-forming bacterium. The inhalational form of anthrax is the most severe and is associated with rapid progression of the disease and the outcome is frequently fatal. Transfer from the respiratory epithelium to regional lymph nodes appears to be an essential early step in the establishment of infection. This transfer is believed to occur by means of carriage within alveolar macrophages following phagocytosis. Therefore, the ability of B. anthracis to transit through the host macrophage or dendritic cell appears to be an early and critical step in B. anthracis pathogenesis. In this work, we examined the cytokine responses to spore infection in mouse primary peritoneal macrophages, in primary human dendritic cells, and during a spore aerosol infection model utilizing the susceptible A/J mouse strain. We demonstrated that both mouse peritoneal macrophages and human dendritic cells exhibited significant intracellular bactericidal activity during the first hours following uptake, providing the necessary time to mount a cytokine response prior to cell lysis. Strong tumor necrosis factor (TNF-{alpha}) and interleukin-6 (IL-6) responses were seen in mouse peritoneal macrophages. In addition to TNF-{alpha} and IL-6, human dendritic cells produced the cytokines IL-1ß, IL-8, and IL-12. A mixture of Th1 and Th2 cytokines were detected in sera obtained from infected animals. In this study, we provide further evidence of an acute cytokine response when cells in culture and mice are infected with B. anthracis spores.

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

Editor: J. T. Barbieri

{dagger} Present address: CBRN Defence Centre, Defence Science and Technology Organisation, Victoria 3207, Australia.

Infection and Immunity, November 2004, p. 6382-6389, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6382-6389.2004




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