Scientific Publications by FDA Staff

Infect Immun 2004 Nov;72(11):6382-9

Cytokine response to infection with Bacillus anthracis spores.

Pickering AK, Osorio M, Lee GM, Grippe VK, Bray M, Merkel TJ

Merkel TJ, US FDA, CBER, DBPAP, Lab Resp & Special Pathogens, Bldg 29,Room 418,29 Lincoln Dr, Bethesda, MD 20892 USA US FDA, CBER, DBPAP, Lab Resp & Special Pathogens, Bethesda, MD 20892 USA US FDA, CBER, DBPAP, Lab Enter & Sexually Transmitted Dis, Bethesda, MD 20892 USA

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-1beta, 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.