Autophagy Controls BCG-Induced Trained Immunity and the Response to Intravesical BCG Therapy for Bladder Cancer

• DOI: 10.1371/journal.ppat.1004485
• Publication Date: 2014-10-30T14:22:58Z
• Authors: Kathrin Buffen; Marije Oosting; Jessica Quintin; Aylwin Ng; Johanneke Kleinni...; Vinod Kumar; Esther van de Vosse; Cisca Wijmenga; Reinout van Crevel; Egbert Oosterwijk; Anne J. Grotenhuis; Sita H. Vermeulen; Lambertus A. Kiem...; Frank L. van de V...; Georgios Chamilos; Ramnik J. Xavier; Jos W. M. van der...; Mihai G. Netea; Leo A. B. Joosten
• Keywords: Reprogramming; BCG vaccine

The anti-tuberculosis-vaccine Bacillus Calmette-Guérin (BCG) is the most widely used vaccine in world. In addition to its effects against tuberculosis, BCG vaccination also induces non-specific beneficial certain forms of malignancy and infections with unrelated pathogens. It has been recently proposed that are mediated through epigenetic reprogramming monocytes, a process called trained immunity. present study we demonstrate autophagy contributes immunity induced by BCG. Pharmacologic inhibition blocked vitro stimuli such as β-glucans or Single nucleotide polymorphisms (SNPs) genes ATG2B (rs3759601) ATG5 (rs2245214) influenced both vivo training effect upon restimulation bacterial fungal stimuli. Furthermore, pharmacologic genetic monocytes at level H3K4 trimethylation. Finally, rs3759601 correlates progression recurrence bladder cancer after intravesical instillation therapy. These findings identify key role for nonspecific protective