AUTHOR=Belhaouane Imène , Hoffmann Eik , Chamaillard Mathias , Brodin Priscille , Machelart Arnaud 

TITLE=Paradoxical Roles of the MAL/Tirap Adaptor in Pathologies

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.569127

DOI=10.3389/fimmu.2020.569127

ISSN=1664-3224

ABSTRACT=<p>Toll-like receptors (TLRs) are at the forefront of pathogen recognition ensuring host fitness and eliciting protective cellular and humoral responses. Signaling pathways downstream of TLRs are tightly regulated for preventing collateral damage and loss of tolerance toward commensals. To trigger effective intracellular signaling, these receptors require the involvement of adaptor proteins. Among these, Toll/Interleukin-1 receptor domain containing adaptor protein (Tirap or MAL) plays an important role in establishing immune responses. Loss of function of MAL was associated with either disease susceptibility or resistance. These opposite effects reveal paradoxical functions of MAL and their importance in containing infectious or non-infectious diseases. In this review, we summarize the current knowledge on the signaling pathways involving MAL in different pathologies and their impact on inducing protective or non-protective responses.</p>