Innate immunity is the first defense system against invading pathogens. Toll-like receptors (TLRs) are well-defined pattern recognition receptors responsible for pathogen recognition and induction of innate immune responses. Since their discovery, TLRs have revolutionized the field of immunology by filling the gap between the initial recognition of pathogens by innate immune cells and the activation of the adaptive immune response. TLRs critically link innate immunity to adaptive immunity by regulating the activation of antigen-presenting cells and key cytokines. Furthermore, recent studies also have shown that TLR signaling can directly regulate the T cell activation, growth, differentiation, development, and function under diverse physiological conditions. This review provides an overview of TLR signaling pathways and their regulators and discusses how TLR signaling, directly and indirectly, regulates cell-mediated immunity. In addition, we also discuss how TLR signaling is critically important in the host’s defense against infectious diseases, autoimmune diseases, and cancer.
A large number of half-Heusler compounds have been recently proposed as three-dimensional (3D) topological insulators (TIs) with tunable physical properties. However, no transport measurements associated with the topological surface states have been observed in these half-Heusler candidates due to the dominating contribution from bulk electrical conductance. Here we show that, by reducing the mobility of bulk carriers, a two-dimensional (2D) weak antilocalization (WAL) effect, one of the hallmarks of topological surface states, was experimentally revealed from the tilted magnetic field dependence of magnetoconductance in a topologically nontrivial semimetal LuPdBi. Besides the observation of a 2D WAL effect, a superconducting transition was revealed at Tc ~ 1.7 K in the same bulk LuPdBi. Quantitative analysis within the framework of a generalized BCS theory leads to the conclusion that the noncentrosymmetric superconductivity of LuPdBi is fully gapped with a possibly unconventional pairing character. The co-existence of superconductivity and the transport signature of topological surface states in the same bulk alloy suggests that LuPdBi represents a very promising candidate as a topological superconductor.
The RIG-I-like receptors (RLRs) are critical for protection against RNA virus infection, and their activities must be stringently controlled to maintain immune homeostasis. Here, we report that leucine-rich repeat containing protein 25 (LRRC25) is a key negative regulator of RLR-mediated type I interferon (IFN) signaling. Upon RNA virus infection, LRRC25 specifically binds to ISG15-associated RIG-I to promote interaction between RIG-I and the autophagic cargo receptor p62 and to mediate RIG-I degradation via selective autophagy. Depletion of either LRRC25 or ISG15 abrogates RIG-I-p62 interaction as well as the autophagic degradation of RIG-I. Collectively, our findings identify a previously unrecognized role of LRRC25 in type I IFN signaling activation by which LRRC25 acts as a secondary receptor to assist RIG-I delivery to autophagosomes for degradation in a p62-dependent manner.
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