Porphyromonas gingivalis selectively up-regulates the HIV-1 coreceptor CCR5 in oral keratinocytes

Giacaman, R.A.; Nobbs A.H.; Ross K.F.; Herzberg M.C.

Keywords: enzyme, biosynthesis, activation, infections, hiv, expression, lipopolysaccharide, antibody, infection, protein, immunodeficiency, cell, antibodies, mutation, bacterial, metabolism, virus, line, humans, keratinocytes, transduction, human, genetics, receptor, strain, cysteine, up-regulation, signal, lysine, rna, proteinase, drug, pathology, antagonism, article, arginine, immunology, keratinocyte, hiv-1, trypsin, toll, mouth, controlled, chemokine, cxcr4, par-2, tlr4, study, 4, 1, priority, toll-like, nonhuman, journal, Receptors,, comparative, RNA,, 2, effect, Receptor,, Messenger, Lipopolysaccharides, unclassified, activated, Porphyromonas, gingivalis, protein,, Endopeptidases, upregulation, Line,, Transformed, adhesin, Adhesins,, Bacteroidaceae, like, CCR5, Lys, gingipain, argingipain,, Lys-gingipain, TLR2, PAR-1

Abstract

Primary infection of oral epithelial cells by HIV-1, if it occurs, could promote systemic infection. Most primary systemic infections are associated with R5-type HIV-1 targeting the R5-specific coreceptor CCR5, which is not usually expressed on oral keratinocytes. Because coinfection with other microbes has been suggested to modulate cellular infection by HIV-1, we hypothesized that oral keratinocytes may up-regulate CCR5 in response to the oral endogenous pathogen Porphyromonas gingivalis by cysteine-protease (gingipains) activation of the protease-activated receptors (PARs) or LPS signaling through the TLRs. The OKF6/TERT-2-immortalized normal human oral keratinocyte line expressed CXCR4, whereas CCR5 was not detectable. When exposed to P. gingivalis ATCC 33277, TERT-2 cells induced greater time-dependent expression of CCR5-specific mRNA and surface coreceptors than CXCR4. By comparing arg- (Rgp) and lys-gingipain (Kgp) mutants, a mutant deficient in both proteases, and the action of trypsin, P. gingivalis Rgp was strongly suggested to cleave PAR-1 and PAR-2 to up-regulate CCR5. CCR5 was also slightly up-regulated by an isogenic gingipain-deficient mutant, suggesting the presence of a nongingipain-mediated mechanism. Purified P. gingivalis LPS also up-regulated CCR5. Blocking TLR2 and TLR4 receptors with Abs attenuated induction of CCR5, suggesting LPS signaling through TLRs. P. gingivalis, therefore, selectively up-regulated CCR5 by two independent signaling pathways, Rgp acting on PAR-1 and PAR-2, and LPS on TLR2 and TLR4. By inducing CCR5 expression, P. gingivalis coinfection could promote selective R5-type HIV-1 infection of oral keratinocytes.

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Título según SCOPUS: Porphyromonas gingivalis selectively up-regulates the HIV-1 coreceptor CCR5 in oral keratinocytes
Título de la Revista: JOURNAL OF IMMUNOLOGY
Volumen: 179
Número: 4
Editorial: AMER ASSOC IMMUNOLOGISTS
Fecha de publicación: 2007
Página de inicio: 2542
Página final: 2550
Idioma: eng
URL: http://www.scopus.com/inward/record.url?eid=2-s2.0-34848854303&partnerID=q2rCbXpz
Notas: SCOPUS