Idelalisib and pneumococcal infection induce distinct transcriptional responses in mouse precision-cut lung slices

Idelalisib has excellent activity in management of chronic lymphocytic leukemia and follicular lymphoma while inducing serious microbial pneumonia in the clinic. To understand the mechanisms of Idelalisib-induced infection risk, we performed RNAseq analyses on mouse precision-cut lung slices treated with Idelalisib in the absence and presence of human lung pathogen Streptococcus pneumoniae. RNAseq transcriptome profiling identifies distinct response signatures in mouse lung slices in responses to Idelalisib treatment and pneumococcal infection. The expression of genes vital for regulation of transcription, immunity and inflammation, cell proliferation and apoptosis, kinase signaling, metabolism, and extracellular matrix remodeling is significantly modulated by Idelalisib. This study provides a new insight for predicting the immunomodulatory impact of drug candidates on host defense and thereby improving the safety profiling of novel drugs for human respiratory diseases.