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Opsono-Adherence Assay to Evaluate Functional Antibodies in Vaccine Development Against Bacillus anthracis and Other Encapsulated Pathogens
Published on: May 19, 2020
CD14-Mac-1 interactions in Bacillus anthracis spore internalization by macrophages
Claudia Oliva1, Charles L Turnbough, John F Kearney
1Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294-2170, USA.
Abstract:
Anthrax, a potentially lethal disease of animals and humans, is caused by the Gram-positive spore-forming bacterium Bacillus anthracis. The outermost exosporium layer of B. anthracis spores contains an external hair-like nap formed by the glycoprotein BclA. Recognition of BclA by the integrin Mac-1 promotes spore uptake by professional phagocytes, resulting in the carriage of spores to sites of spore germination and bacterial growth in distant lymphoid organs. We show that CD14 binds to rhamnose residues of BclA and acts as a coreceptor for spore binding by Mac-1. In this process, CD14 induces signals involving TLR2 and PI3k that promote inside-out activation of Mac-1, thereby enhancing spore internalization by macrophages. As observed with mice lacking Mac-1, CD14(-/-) mice are also more resistant than wild-type mice to infection by B. anthracis spores. Additionally, after B. anthracis spore challenge of CD14(-/-) mice, interference with the CD14-mediated signaling pathways results in increased mortality. Our results show that the binding and uptake of B. anthracis spores by phagocytic cells is a dynamic process and involves multiple receptors and signaling pathways.
Insights
CD14 acts as a coreceptor for Bacillus anthracis spore uptake by macrophages, enhancing bacterial entry. CD14 signaling is crucial for controlling anthrax infection, as its absence increases mortality.
Area of Science:
- Immunology
- Microbiology
- Bacterial Pathogenesis
Background:
- Anthrax is a severe disease caused by Bacillus anthracis.
- The B. anthracis spore surface glycoprotein BclA is key for host cell recognition.
- Integrin Mac-1 mediates phagocyte uptake of B. anthracis spores.
Purpose of the Study:
- To investigate the role of CD14 in Bacillus anthracis spore uptake.
- To elucidate the signaling pathways involved in CD14-mediated spore internalization.
- To assess the in vivo relevance of CD14 in anthrax infection.
Main Methods:
- In vitro binding assays using recombinant BclA and CD14.
- Macrophage uptake studies with fluorescently labeled B. anthracis spores.
- Flow cytometry and Western blotting to analyze signaling pathways (TLR2, PI3k).
- In vivo infection models using wild-type, CD14(-/-), and Mac-1(-/-) mice.
Main Results:
- CD14 binds to rhamnose residues on BclA, acting as a coreceptor for Mac-1.
- CD14 engagement triggers TLR2 and PI3k signaling, leading to Mac-1 activation.
- CD14 deficiency enhances resistance to B. anthracis infection in mice.
- Interference with CD14 signaling pathways increases mortality in CD14(-/-) mice.
Conclusions:
- CD14 is a crucial coreceptor for Bacillus anthracis spore uptake by phagocytes.
- The CD14-Mac-1 interaction is a dynamic process involving TLR2 and PI3k signaling.
- CD14 plays a significant role in host defense against anthrax, influencing disease outcome.
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