title: Effects of caspofungin, Candida albicans and Aspergillus fumigatus on toll-like receptor 9 of GM-CSF-stimulated PMNs.
abstract: The possible involvement of Toll-like receptors (TLRs) 1, 2, 4 and 9 in the interaction of antifungal drugs with polymorphonuclear neutrophils (PMNs) in response to Aspergillus fumigatus and Candida albicans as stimuli was investigated. Caspofungin revealed the broadest capacity to enable C. albicans and A. fumigatus to stimulate TLR upregulation, TLR 2 by A. fumigatus and TLRs 4, 9 by C. albicans. Conventional amphotericin B (cAMB) stimulated only A. fumigatus to induce TLRs 2 and 4 upregulation; voriconazole stimulated A. fumigatus and fluconazole C. albicans to induce TLR 9 upregulation. For cAMB, only TLR 9 was upregulated by A. fumigatus, whereas in the case of voriconazole, TLRs 2, 4, 9 were upregulated. Caspofungin revealed the broadest capacity: C. albicans was stimulated to upregulate TLRs at least at one of the concentrations, and A. fumigatus was stimulated to upregulate TLRs 2, 4. TLR 9 was upregulated two to three fold by all antifungal drugs on protein, except for fluconazole at the RNA level. Candida albicans preincubated with caspofungin has additional effects on CD11b expression and IL8 chemotaxis in CpG-DNA-stimulated PMNs. These results indicate a relevant upregulation with a functional relevance of TLR 9 in the presence of C. albicans strains preincubated with caspofungin at three concentrations.
authors.affiliation: Pediatric Pulmonology, Department of Pediatrics III, Cystic Fibrosis Centre and Infectious Diseases, University Heidelberg, Heidelberg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Salvenmoser
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Seidler
authors.forename: Alexander
authors.initials: A
authors.lastname: Dalpke
authors.forename: Frank-Michael C
authors.initials: FM
authors.lastname: Müller
mesh_terms: D000666:Amphotericin B / Q000378:metabolism; D000935:Antifungal Agents / Q000378:metabolism; D001232:Aspergillus fumigatus / Q000276:immunology*; D039481:CD11b Antigen / Q000096:biosynthesis; D002176:Candida albicans / Q000276:immunology*; D000077336:Caspofungin; D002478:Cells, Cultured; D054714:Echinocandins / Q000378:metabolism*; D015870:Gene Expression; D020869:Gene Expression Profiling; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism; D055666:Lipopeptides; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D011743:Pyrimidines / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051193:Toll-Like Receptors / Q000096:biosynthesis* / Q000276:immunology; D014230:Triazoles / Q000378:metabolism; D015854:Up-Regulation; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D039481:CD11b Antigen; C508606:CXCL8 protein, human; D054714:Echinocandins; C509295:ITGAM protein, human; D007155:Immunologic Factors; D016209:Interleukin-8; D055666:Lipopeptides; D011743:Pyrimidines; D051193:Toll-Like Receptors; D014230:Triazoles; D000666:Amphotericin B; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000077336:Caspofungin; D065819:Voriconazole