Abstract
The causative agent of anthrax, Bacillus anthracis, is capable of circumventing the humoral and innate immune defense of the host and modulating the blood chemistry in circulation to initiate a productive infection. It has been shown that the pathogen employs a number of strategies against immune cells using secreted pathogenic factors such as toxins. However, interference of B. anthracis with the innate immune system through specific interaction of the spore surface with host proteins such as the complement system has heretofore attracted little attention. In order to assess the mechanisms by which B. anthracis evades the defense system, we employed a proteomic analysis to identify human serum proteins interacting with B. anthracis spores, and found that plasminogen (PLG) is a major surface-bound protein. PLG efficiently bound to spores in a lysine- and exosporium-dependent manner. We identified α-enolase and elongation factor tu as PLG receptors. PLG-bound spores were capable of exhibiting anti-opsonic properties by cleaving C3b molecules in vitro and in rabbit bronchoalveolar lavage fluid, resulting in a decrease in macrophage phagocytosis. Our findings represent a step forward in understanding the mechanisms involved in the evasion of innate immunity by B. anthracis through recruitment of PLG resulting in the enhancement of anti-complement and anti-opsonization properties of the pathogen.
Highlights
Bacillus anthracis, the causative organism of anthrax, is a sporeforming Gram-positive bacterium
We have found that B. anthracis spores bind a number of human serum proteins that are involved in humoral and innate immunity
Deposition of complement C3 onto B. anthracis spores has been reported to be required for opsonin-dependent phagocytosis by macrophages [21]
Summary
The causative organism of anthrax, is a sporeforming Gram-positive bacterium. In order to initiate a productive infection, B. anthracis needs to circumvent the innate protective response of the host. Lethal and edema toxins secreted along with other virulence factors such as hemolysins within the phagosomal compartment of macrophages allow the bacteria to resist being killed and to escape from the phagocytes [3]. Cleavage of mitogen-activated protein kinase kinases by lethal toxin seems to play a central role in the immunosuppressive capacity of B. anthracis to induce necrosis or apoptosis of macrophages [4] and to inhibit responses of dendritic and T cells [5,6,7]. Interference of B. anthracis with the innate immune system through specific interaction of the spore surface with the host proteins such as the complement system has heretofore attracted little attention
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