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Infect. Immun. doi:10.1128/IAI.00314-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Human CD18 is the functional receptor for Aggregatibacter actinomycetemcomitans leukotoxin

Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, Minnesota 55108; Department of Oral Biology, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103

^* To whom correspondence should be addressed. Email: mahes001{at}umn.edu.

	Abstract

Aggregatibacter (Actinobacillus) actinomycetemcomitans is the causative organism of localized aggressive periodontitis (LAP), a rapidly progressing degenerative disease of the gingival and periodontal ligaments, and also implicated in causing subacute infective endocarditis in humans. The bacterium produces a variety of virulence factors including an exotoxic leukotoxin (LtxA) that is a member of the repeats-in-toxin (RTX) family of bacterial cytolysins. LtxA exhibits a unique specificity to macrophages and polymorphonuclear cells of humans and other primates. Human lymphocyte function associated antigen-1 (LFA-1) has been implicated as the putative receptor for LtxA. Human LFA-1 comprises the CD11a and CD18 subunits. It is not clear however, which of its subunits serves as the functional receptor that confers species specific susceptibility to LtxA. Here we demonstrate that the human CD18 is the receptor for LtxA based on experiments performed with chimeric 2 integrins recombinantly expressed in a cell line that is resistant to LtxA effects. In addition, we show that the cysteine-rich tandem repeats encompassing integrin-epidermal growth factor like domains (I-EGF) -2, -3 and -4 of the extracellular region of human CD18 are critical for conferring susceptibility to LtxA induced biological effects.