Induction of nuclear factor- kappa B and c-Jun/activator protein-1 via toll-like receptor 2 in macrophages by antimycotic-treated Candida albicans.
We examined the role of Toll-like receptors (TLRs) by using TLR2-deficient (TLR2(-/-)), TLR4-defective (TLR4(d/d)), and double-knockout murine macrophages and human embryonic kidney (HEK) 293 cells transfected with human TLR2 or TLR4 expression plasmids after stimulation with different preparations of the human pathogenic fungus Candida albicans. Compared with wild-type macrophages, TLR2(-/-) and TLR4(d/d) macrophages had impaired recognition of viable C. albicans, whereas antimycotic (AM)-treated C. albicans solely used TLR2 in a TLR4- and interferon- gamma -independent manner. In human HEK293 cells, AM-treated C. albicans elicited mainly TLR2-dependent activation. The differences in responsiveness to viable C. albicans, compared with C. albicans treated with cytoplasmic membrane-interacting AMs, suggest specific recognition of different pathogen-associated patterns by TLRs in innate antifungal responses. Our analyses of signal transduction after stimulation of wild-type macrophages with AM-treated C. albicans demonstrated involvement of the transcription factors nuclear factor- kappa B and c-Jun/activator protein-1 and of the mitogen-activated protein kinases p38, extracellular-related kinase, and c-Jun NH(2)-terminal kinase.
Roeder
Alexander
A
Department of Dermatology, Ludwig-Maximilian-University, Munich, Germany.
Kirschning
Carsten J
CJ
Schaller
Martin
M
Weindl
Gunther
G
Wagner
Hermann
H
Korting
Hans-Christian
HC
Rupec
Rudolf A
RA
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D018808:Transcription Factor AP-1 / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D000935:Antifungal Agents; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases