Human beta-defensins: differential activity against candidal species and regulation by Candida albicans.
Oral epithelial cell-derived human beta-defensins-1, -2, and -3 participate in innate immune responses against Candida. We hypothesized that these peptides utilize several mechanisms for protection. Recombinant hBD-1 and -2 were produced with the use of an insect cell/baculovirus expression system, while rhBD-3 was expressed as a fusion protein in E. coli. RhBD-2 and -3 were more effective at killing the candidal species at low micromolar concentrations than was rhBD-1, except for C. glabrata. While this species was relatively resistant to rhBD fungicidal activity, its adherence to oral epithelial cells was strain-specifically inhibited by the rhBDs. C. albicans hyphae were important in regulating hBD2 and -3 mRNA expression in primary human oral epithelial cells. Confocal microscopy of rhBD-2-challenged C. albicans suggests disruption of the fungal membrane. Results support the hypothesis that hBDs control fungal colonization through hyphal induction, direct fungicidal activity, and inhibition of candidal adherence.
Feng
Z
Z
Department of Biological Sciences, Case Western Reserve University School of Dental Medicine, 10900 Euclid Avenue, Cleveland, OH 44106-4905, USA.
Jiang
B
B
Chandra
J
J
Ghannoum
M
M
Nelson
S
S
Weinberg
A
A
D000890:Anti-Infective Agents / Q000494:pharmacology*; D002175:Candida / Q000145:classification / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development; D041221:Candida glabrata / Q000187:drug effects / Q000254:growth & development; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D025141:Drug Resistance, Fungal; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D018613:Microscopy, Confocal; D009061:Mouth Mucosa / Q000166:cytology; D011994:Recombinant Proteins; D023083:beta-Defensins / Q000494:pharmacology*
D000890:Anti-Infective Agents; C406407:DEFB1 protein, human; C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D011994:Recombinant Proteins; D023083:beta-Defensins