Caspofungin enhances antifungal immunity in human blood through transcriptional reprogramming

This study investigates how the echinocandin antifungal drug caspofungin (CAS) modulates early immune responses during Candida albicans bloodstream infection. Echinocandin-susceptible (ECHS/FKSwt) and echinocandin-resistant (ECHR/FKSmut) C. albicans candidemia strains were used to determine whether CAS-induced host transcriptional changes depend on fungal susceptibility. Because immune modulation by CAS appears highly context dependent, we used an ex vivo human whole-blood system to capture physiologically relevant immune-pathogen interactions. Fresh human whole blood from healthy donors was infected ex vivo with either an echinocandin-susceptible (ECHS/FKSwt) or echinocandin-resistant (ECHR/FKSmut) C. albicans isolate. Samples were treated with CAS or left untreated as controls. After a defined incubation period, leukocyte RNA was isolated. Human mRNA sequencing was performed by Novogene (Novogene GmbH, Munich). RNA quality was assessed prior to library preparation, and globin mRNA was removed using GlobinClear. Sequencing was performed on an Illumina platform using 150 bp paired-end reads. Raw sequencing data underwent standard quality control, including removal of adapter sequences and low-quality reads. Clean reads were aligned to the human reference genome, and gene expression was quantified. Differential expression analyses were performed to identify host transcriptional responses to CAS during infections with susceptible versus resistant C. albicans strains.