title: Voriconazole inhibits fungal growth without impairing antigen presentation or T-cell activation.
abstract: Invasive aspergillosis (IA) is the most common life-threatening invasive mold infection worldwide. The principal therapy for IA is amphotericin B, despite its known toxicity and immunosuppressive side effects. Studies in animal models of IA suggest a role for T lymphocytes in the pathology of the disease, although the precise role for Aspergillus-specific T cells remains undefined. The isolation and characterization of T lymphocytes in animal models of IA are hampered by the rapid outgrowth of the fungus in cultures derived from infected organs. In the present study, we tested the abilities of the antifungal drugs caspofungin acetate and voriconazole to inhibit fungal growth in vitro as a means of maintaining cultures of T cells from Aspergillus-infected mice. We demonstrate that while both antifungal drugs are inhibitory, only voriconazole completely inhibited fungal growth, allowing long-term maintenance of T-cell cultures. In addition, voriconazole had no inhibitory effect on the activation and maturation of dendritic cells or the proliferation of T lymphocytes. Thus, voriconazole appears to be a promising agent for use in in vitro studies of Aspergillus-specific T lymphocytes in animal models of IA.
authors.affiliation: Laboratory of Antimicrobial Immunity, Immunology Program, and Infectious Disease Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Van Epps
authors.forename: Marta
authors.initials: M
authors.lastname: Feldmesser
authors.forename: Eric G
authors.initials: EG
authors.lastname: Pamer
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D017951:Antigen Presentation / Q000187:drug effects* / Q000276:immunology; D001228:Aspergillosis / Q000188:drug therapy / Q000276:immunology; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000254:growth & development; D000077336:Caspofungin; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D054714:Echinocandins; D055666:Lipopeptides; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010455:Peptides; D010456:Peptides, Cyclic; D011743:Pyrimidines / Q000494:pharmacology*; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014230:Triazoles / Q000494:pharmacology*; D065819:Voriconazole
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D010455:Peptides; D010456:Peptides, Cyclic; D011743:Pyrimidines; D014230:Triazoles; D000077336:Caspofungin; D065819:Voriconazole