Implications of Toll-like receptors in Ebola infection.

INTRODUCTION: The potential roles of toll-like receptors (TLRs) in immunopathogenesis of Ebola virus disease should be unraveled to provoke possible prophylactic or therapeutic implications of TLRs for EVD. Areas covered: The Ebola virus (EBOV) infection virtually paralyses all the main mechanisms responsible for induction of type I interferon (IFN-I) response. To summarize, EBOV infection interferes with: a) the TIR-domain-containing adapter-inducing interferon-β (TRIF) pathway that is mediated by TLR3 and TLR4 signaling; b) the interferon regulatory factor 7 (IRF7) pathway that is stimulated by TLR7 and TLR9; c) the intracellular signaling that is induced by retinoic acid-inducible gene 1 (RIG-I)-like receptors (RLRs); and d) the autocrine/paracrine feedback loop that is mediated by the IFN-stimulated gene factor 3 (ISGF3) complex. Upon infection with EBOV infection, TLR4 plays a key role in production of proinflammatory mediators. Expert opinion: It is theoretically possible that use of TLRs 3, 4, 7, and 9 agonists would be beneficial to improve the IFN-I response, despite their systemic side effects. Also, antagonist of TLR4 can be utilized to prevent production of proinflammatory cytokines. Additionally, it is highly recommended to design future investigations aimed at determining if the utilization of IFN-I would be beneficial for prophylactic/therapeutic programs of Ebola.