Pathogenesis of Bacillus anthracis in a murine model of inhalation anthrax

Inhalation anthrax consists of two stages during which host and bacterial factors may play a role. The first stage occurs in the lung where each factor, may contribute to survival, germination or the ability of the spore to access the draining lymph nodes. The second major stage is after dissemination into the blood stream where these factors may affect the ability of the bacilli to colonize and damage vital organs throughout the host. The present report examines both host factors and the primary bacterial virulence factors during the pathogenesis of a pulmonary anthrax infection.; B. anthracis is known to produce at least three primary virulence factors, lethal toxin, edema toxin, and a capsule. We show that a strain carrying both virulence plasmids but deleted for capBCAD is highly attenuated in a mouse model for inhalation anthrax as demonstrated by a decreased LD50 and inability to disseminate. Whereas, mutants lacking one or more of the structural toxin genes, pagA, lef, and cya, displayed similar LD50 's and disseminated from the lung to the spleen at rates similar to the virulent parental strain.; Host immune cells such as alveolar macrophages have long been thought to play a primary role in the pathogenesis of a B. anthracis infection. It is believed upon inhalation B. anthracis spores are phagocytosed by alveolar macrophages. Recently it has been called into question as to whether macrophages serve as a conduit to the lymph node or play a role in limiting infection. We show that when AMs are depleted there is no significant difference in the LD50 when compared to controls. Furthermore, spores gain access the lymph nodes at the same time independent of the presence or absence of AMs. When alveolar macrophages were depleted a large increase in CFU was noted in the spleen only after a population of bacteria was established in the lymph node. Once a small number of fully encapsulated bacteria enter the blood stream we demonstrate through systemic macrophage depletion, that the macrophages unable contain the infection. This indicates macrophages only play a role in limiting dissemination of the bacteria from the lymph node.