Human CD18 is the functional receptor for Aggregatibacter actinomycetemcomitans leukotoxin

T. Dileepan, Scott Kachlany, N. V. Balashova, J. Patel, S. K. Maheswaran

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Aggregatibacter (Actinobacillus) actinomycetemcomitans is the causative organism of localized aggressive periodontitis, a rapidly progressing degenerative disease of the gingival and periodontal ligaments, and is 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 β2-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 2, 3, and 4 of the extracellular region of human CD18 are critical for conferring susceptibility to LtxA-induced biological effects.

Original languageEnglish (US)
Pages (from-to)4851-4856
Number of pages6
JournalInfection and immunity
Volume75
Issue number10
DOIs
StatePublished - Oct 1 2007

Fingerprint

Aggregatibacter actinomycetemcomitans
Lymphocyte Function-Associated Antigen-1
Integrins
Gingival Diseases
Aggressive Periodontitis
Bacterial Toxins
Periodontal Ligament
Tandem Repeat Sequences
Cytotoxins
Virulence Factors
Endocarditis
Epidermal Growth Factor
Primates
Cysteine
leukotoxin
Macrophages
Bacteria
Cell Line

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Dileepan, T. ; Kachlany, Scott ; Balashova, N. V. ; Patel, J. ; Maheswaran, S. K. / Human CD18 is the functional receptor for Aggregatibacter actinomycetemcomitans leukotoxin. In: Infection and immunity. 2007 ; Vol. 75, No. 10. pp. 4851-4856.
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Human CD18 is the functional receptor for Aggregatibacter actinomycetemcomitans leukotoxin. / Dileepan, T.; Kachlany, Scott; Balashova, N. V.; Patel, J.; Maheswaran, S. K.

In: Infection and immunity, Vol. 75, No. 10, 01.10.2007, p. 4851-4856.

Research output: Contribution to journalArticle

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AU - Kachlany, Scott

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