Summary: Toll‐like receptor‐3 (TLR‐3) recognizes double‐stranded RNA and induces multiple intracellular events responsible for innate anti‐viral immunity against a number of viral infections. Activation of TLR‐3 inhibits human immunodeficiency virus (HIV) replication, but the mechanism(s) underlying the action of TLR‐3 activation on HIV are largely unknown. Here we demonstrate that treatment of monocyte‐derived macrophages with poly I:C, a synthetic ligand for TLR‐3, significantly inhibited HIV infection and replication. Investigation of the mechanisms showed that TLR‐3 activation resulted in the induction of type I interferon inducible antiviral factors, including APOBEC3G and tetherin, the newly identified anti‐HIV cellular proteins. In addition, poly I:C‐treated macrophages expressed increased levels of CC chemokines, the ligands for CCR5. Furthermore, TLR‐3 activation in macrophages induced the expression of cellular microRNAs (miRNA‐28, ‐125b, ‐150, ‐223 and ‐382), the newly identified intracellular HIV restriction factors. These findings indicate that TLR‐3‐mediated induction of multiple anti‐HIV factors should be beneficial for the treatment of HIV disease where innate immune responses are compromised by the virus.

Toll-like receptor 3 (TLR3) plays a critical role in initiating type I IFN-mediated innate immunity against viral infections. TLR3 recognizes various forms of double stranded (ds) RNA, including viral dsRNA and a synthetic mimic of dsRNA, poly I:C, which has been used extensively as a TLR3 ligand to induce antiviral immunity. The activation efficiency of TLR3 by poly I:C is influenced by various factors, including size of the ligands, delivery methods and cell types. In this study, we examined the stimulatory effect of two commercially-available poly I:Cs [high molecular mass (HMM) and low molecular mass (LMM)] on TLR3 activation in various human cell types by determining the induction of type I and type III IFNs, as well as the antiviral effect. We demonstrated that the direct addition of both HMM- and LMM-poly I:C to the cultures of primary macrophages or a neuroplastoma cell line could activate TLR3. However, the transfection of poly I:C was necessary to induce TLR3 activation in other cell types studied. In all the cell lines tested, the efficiency of TLR3 activation by HMM-poly I:C was significantly higher than that by LMM-poly I:C. These observations indicate the importance and necessity of developing effective TLR3 ligands for antiviral therapy.

The use of animal models has been invaluable for studying the pathogenesis of Mycobacterium tuberculosis infection, as well as for testing the efficacy of vaccines and drug regimens for tuberculosis. Among the applied animal models, the nonhuman primates, particularly macaques, share the greatest anatomical and physiological similarities with humans. As such, macaque models have been used for investigating tuberculosis pathogenesis and preclinical testing of drugs and vaccines. This review focuses on published major studies which illustrate how the rhesus and cynomolgus macaques have enriched and may continue to advance the field of global tuberculosis research.

(−)-Epigallocatechin gallate (EGCG) is a major polyphenol component of green tea that has antioxidant activities. Lipopolysaccharide (LPS) induces inflammatory cytokine production and impairs blood–brain barrier (BBB) integrity. We examined the effect of EGCG on LPS-induced expression of the inflammatory cytokines in human cerebral microvascular endothelial cells (hCMECs) and BBB permeability.