Updating Perspectives on the Initiation of Bacillus anthracisGrowth and Dissemination through Its Host

ABSTRACTSince 1957, it has been proposed that the dissemination of inhalational anthrax required spores to be transported from the lumena of the lungs into the lymphatic system. In 2002, this idea was expanded to state that alveolar macrophages act as a “Trojan horse” capable of transporting spores across the lung epithelium into draining mediastinal lymph nodes. Since then, the Trojan horse model of dissemination has become the most widely cited model of inhalational infection as well as the focus of the majority of studies aiming to understand events initiating inhalational anthrax infections. However, recent observations derived from animal models of Bacillus anthracisinfection are inconsistent with aspects of the Trojan horse model and imply that bacterial dissemination patterns during inhalational infection may be more similar to the cutaneous and gastrointestinal forms than previously thought. In light of these studies, it is of significant importance to reassess the mechanisms of inhalational anthrax dissemination, since it is this form of anthrax that is most lethal and of greatest concern when B. anthracisis weaponized. Here we propose a new “jailbreak” model of B. anthracisdissemination which applies to the dissemination of all common manifestations of the disease anthrax. The proposed model impacts the field by deemphasizing the role of host cells as conduits for dissemination and increasing the role of phagocytes as central players in innate defenses, while moving the focus toward interactions between B. anthracisand lymphoid and epithelial tissues.