Idelalisib Impairs TREM-1 and TLR Mediated Neutrophil Activation

Introduction: Polymorphonuclear neutrophils (PMN) play an essential role in innate inflammatory processes. Their functions are strictly regulated and many activating / inhibiting mechanisms along with their pathways are only incompletely understood. Besides toll-like receptors (TLR) and NOD-like receptors (NLR), triggering receptor expressed on myeloid cells (TREM)-1 is implicated in innate immune activation of these cells and plays a role in infectious as well as non-infectious conditions. Activation of TREM-1 results in release of pro-inflammatory chemokines and cytokines, increased surface expression of cell activation markers and degranulation. In TREM-1 downstream pathways and regulation of TREM-1 expression protein kinase A (PKA), phosphatidylinositide 3-kinase (PI3K), mitogen-activated protein kinases (p38 MAPK) and phospholipase C (PLC) are involved.