Distinct roles of TNF-related apoptosis-inducing ligand (TRAIL) in viral and bacterial infections: from pathogenesis to pathogen clearance

Apoptotic death of different cells observed during infection is thought to limit overwhelming inflammation in response to microbial challenge. However, the underlying apoptotic death mechanisms have not been well defined. Tumor necrosis factor (TNF) related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein belonging to the TNF superfamily, which is involved not only in tumor growth suppression but in infection control and also in the regulation of both innate and adaptive immune responses. In this review, we have summarized data of recent studies on the influence of the TRAIL/TRAIL receptor (TRAIL-R) system on the development of viral and bacterial infections. TRAIL may have a dual function in the immune system being able to kill infected cells and also to participate in the pathogenesis of multiple infections. Moreover, many pathogens have evolved mechanisms to manipulate TRAIL signaling thus increasing pathogen replication. Present data highlight an essential role for the TRAIL/TRAIL-R system in the regulation and modulation of apoptosis and show that TRAIL has distinct roles in pathogenesis and pathogen elimination. Knowledge of the factors that determine whether TRAIL is helpful or harmful supposes its potential therapeutic implications that are only beginning to be explored.