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Published on: February 28, 2019
Human CD18 is the functional receptor for Aggregatibacter actinomycetemcomitans leukotoxin
T Dileepan1, S C Kachlany, N V Balashova
1Department of Veterinary and Biomedical Sciences, University of Minnesota, 1971 Commonwealth Avenue, St. Paul, MN 55108, USA.
Aggregatibacter actinomycetemcomitans leukotoxin (LtxA) targets immune cells. Researchers identified human CD18 as the specific receptor for LtxA, revealing critical domains for LtxA
Area of Science:
- Microbiology
- Immunology
- Molecular Biology
Background:
- Aggregatibacter actinomycetemcomitans causes aggressive periodontitis and endocarditis.
- Leukotoxin (LtxA) is a key virulence factor targeting immune cells.
- Lymphocyte function-associated antigen 1 (LFA-1) is the suspected LtxA receptor.
Purpose of the Study:
- Identify the specific subunit of LFA-1 that functions as the LtxA receptor.
- Determine the regions of the receptor critical for LtxA binding and activity.
Main Methods:
- Utilized chimeric beta2-integrins expressed in LtxA-resistant cells.
- Investigated LtxA binding and biological effects on engineered cells.
Main Results:
- Demonstrated that human CD18 is the functional receptor for LtxA.
- Identified specific extracellular domains (integrin-epidermal growth factor-like domains 2, 3, and 4) of CD18 as critical for LtxA interaction.
- Showed these domains confer species-specific susceptibility to LtxA.
Conclusions:
- Human CD18 is the primary receptor for Aggregatibacter actinomycetemcomitans leukotoxin.
- Specific extracellular domains of CD18 are essential for LtxA's cytotoxic effects.
- Findings advance understanding of bacterial pathogenesis and host-pathogen interactions.
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