Abstract

Inhalational anthrax is established after inhaled Bacillus anthracis spores are transported to the lung associated lymph nodes. Dendritic cells (CD11c+ cells) located in the lungs are phagocytes that maintain many capabilities consistent with transport. This study investigates the role of dendritic cells as conduits of spores from the lung to the draining lymph nodes. The intratracheally spore-challenged mouse model of inhalational anthrax was utilized to investigate in vivo activities of CD11c+ cells. FITC labeled spores were delivered to the lungs of mice. Subsequently lung associated lymph nodes were isolated after infection and CD11c+ cells were found in association with the labeled spores. Further investigation of CD11c+ cells in early anthrax events was facilitated by use of the CD11c-diphtheria toxin (DT) receptor-green fluorescent protein transgenic mice in which CD11c+ cells can be transiently depleted by treatment with DT. We found that the presence of CD11c+ cells was necessary for efficient traffic of the spore to lung associated lymph nodes at early times after infection. Cultured dendritic cells were used to determine that these cells are capable of B. anthracis spore phagocytosis, and support germination and outgrowth. This data demonstrates that CD11c+ cells are likely carriers of B. anthracis spores from the point of inhalation in the lung to the lung associated lymph nodes. The cultured dendritic cell allows for spore germination and outgrowth supporting the concept that the CD11c+ cell responsible for this function can be a dendritic cell.

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