Roles of Macrophages and Neutrophils in the Early Host Response to Bacillus anthracis Spores in a Mouse Model of Infection

摘要

The development of new approaches to combat anthrax requires that the pathogenesis and host response to Bacillus anthracis spores be better understood. We investigated the roles that macrophages and neutrophils play in the progression of a B. anthracis infection. In our in vivo model, mice were treated with a macrophage-depletion agent (liposome encapsulated clodronate) or with a neutrophil-depletion agent (cyclophosphamide or the rat anti-mouse granulocyte monoclonal antibody RB6-8C5) and the animals were then infected intraperitoneally or by aerosol challenge with fully virulent, ungerminated B. anthracis strain Ames spores. The macrophage-depleted mice were significantly more susceptible to the ensuing infection than the saline-pretreated mice, whereas the differences observed between the neutropenic mice and the saline- pretreated controls were generally insignificant. We also found that augmenting peritoneal neutrophil populations before spore challenge did not increase resistance of the mice to infection. In addition, the bacterial load in macrophage-depleted mice was significantly greater and appeared significantly sooner than that observed in the saline-pretreated mice. In contrast, the bacterial load in the neutropenic mice was comparable to that of the saline- pretreated mice. These data suggest that, in our model, neutrophils play a relatively minor role in the early host-response to infection with B. anthracis Ames spores, whereas macrophages play a more dominant role in early host defenses against an infection by B. anthracis spores.