Journal article
CD14-Mac-1 interactions in Bacillus anthracis spore internalization by macrophages
Proceedings of the National Academy of Sciences - PNAS, Vol.106(33), pp.13957-13962
08/18/2009
DOI: 10.1073/pnas.0902392106
PMCID: PMC2729002
PMID: 19666536
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.
Details
- Title: Subtitle
- CD14-Mac-1 interactions in Bacillus anthracis spore internalization by macrophages
- Creators
- Claudia Oliva - University of Alabama at BirminghamCharles L. Turnbough - Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USAJohn F. Kearney - Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.106(33), pp.13957-13962
- Publisher
- Natl Acad Sciences
- DOI
- 10.1073/pnas.0902392106
- PMID
- 19666536
- PMCID
- PMC2729002
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Number of pages
- 6
- Grant note
- AI057699-03 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P01AI057699 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Language
- English
- Date published
- 08/18/2009
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984313069402771
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