Effects of caspofungin, Candida albicans and Aspergillus fumigatus on toll-like receptor 9 of GM-CSF-stimulated PMNs

FEMS Immunology and Medical Microbiology
Stefanie SalvenmoserFrank-Michael C Müller

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 ...Continue Reading

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Citations

May 31, 2012·Antimicrobial Agents and Chemotherapy·Silvia MorettiFranco Aversa
Nov 23, 2013·The Journal of Antimicrobial Chemotherapy·Silvia MorettiLucia Pitzurra
Nov 18, 2015·Immunological Investigations·Kausik Datta, Mawieh Hamad
Jul 21, 2015·Expert Opinion on Therapeutic Targets·Nassim MatinNima Rezaei
Oct 12, 2011·Immunological Investigations·Maria SimitsopoulouThomas J Walsh
Sep 10, 2014·Current Opinion in Pharmacology·Giuliana BancheAnna Maria Cuffini
Mar 29, 2014·Frontiers in Microbiology·Mircea R MihuJoshua D Nosanchuk

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