Perspectives on intracellular perception of plant viruses

The intracellular nucleotide-binding domain leucine-rich repeat (NLR) class of immune receptors plays an important role in plant viral defence. Plant NLRs recognize viruses through direct or indirect association of viral proteins, triggering a downstream defence response to prevent viral proliferation and movement within the plant. This review focuses on current knowledge of intracellular perception of viral pathogens, activation of NLRs and the downstream signalling components involved in plant viral defence.     

The Mitochondrial Protein NLRX1 Controls the Balance between Extrinsic and Intrinsic Apoptosis

NLRX1 is a mitochondrial Nod-like receptor (NLR) protein whose function remains enigmatic. Here, we observed that NLRX1 expression was glucose-regulated and blunted by SV40 transformation. In transformed but not primary murine embryonic fibroblasts, NLRX1 expression mediated resistance to an extrinsic apoptotic signal, whereas conferring susceptibility to intrinsic apoptotic signals, such as glycolysis inhibition, increased cytosolic calcium and endoplasmic reticulum stress. In a murine model of colorectal cancer induced by azoxymethane, NLRX1−/− mice developed fewer tumors than wild type mice. In contrast, in a colitis-associated cancer model combining azoxymethane and dextran sulfate sodium, NLRX1−/− mice developed a more severe pathology likely due to the increased sensitivity to dextran sulfate sodium colitis. Together, these results identify NLRX1 as a critical mitochondrial protein implicated in the regulation of apoptosis in cancer cells. The unique capacity of NLRX1 to regulate the cellular sensitivity toward intrinsic versus extrinsic apoptotic signals suggests a critical role for this protein in numerous physiological processes and pathological conditions.     

TIR domains of plant immune receptors are 2′,3′-cAMP/cGMP synthetases mediating cell death

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Tracking disease resistance deployment in potato breeding by enrichment sequencing

Following the molecular characterisation of functional disease resistance genes in recent years, methods to track and verify the integrity of multiple genes in varieties are needed for crop improvement through resistance stacking. Diagnostic resistance gene enrichment sequencing (dRenSeq) enables the high‐confidence identification and complete sequence validation of known functional resistance genes in crops. As demonstrated for tetraploid potato varieties, the methodology is more robust and cost‐effective in monitoring resistances than whole‐genome sequencing and can be used to appraise (trans) gene integrity efficiently. All currently known NB‐LRRs effective against viruses, nematodes and the late blight pathogen Phytophthora infestans can be tracked with dRenSeq in potato and hitherto unknown polymorphisms have been identified. The methodology provides a means to improve the speed and efficiency of future disease resistance breeding in crops by directing parental and progeny selection towards effective combinations of resistance genes.     

The NLRP3 Inflammasome Renders Cell Death Pro-inflammatory

NLRP3 is the most studied inflammasome sensor due to its crucial involvement in sterile and infection-triggered inflammation. Although its molecular mode of activation remains to be defined, it is well established that low intracellular potassium concentrations result in its activation. This functionality allows the classical NLRP3 pathway to serve as a highly sensitive, but non-specific surveillance mechanism responding to any type of perturbation that breaches plasma membrane integrity and the associated potassium gradient across the membrane. Here, we review our current knowledge on potassium efflux-dependent NLRP3 activation, with a special focus on how major cell death programs are rendered pro-inflammatory by secondary NLRP3 activation. Apart from the “alternative inflammasome” as the major exception to the rule, this connection explains the fundamental importance of NLRP3 in cell death-associated inflammation and firmly establishes NLRP3 as a principal surveillance mechanism of cellular integrity.     

NOD样受体在炎症反应中的调控作用

天然免疫(innate immunity)是机体免疫系统直接抵御病原体入侵的最初阶段,通过机体自身的特异性模式识别受体(pattern-recognition receptors,PRRs)来识别病原体特有的保守结构病原相关分子模式(pathogen-associated molecular patterns,PAMPs)。细胞内NOD样受体(NLRs)是胞浆型PRRs中的一个重要家族,病原体侵袭细胞可上调其表达,启动机体的免疫应答和炎症反应,在机体天然免疫应答中发挥独特的功能。最近有研究证明,NLRs的突变与一些人类免疫性疾病相关,并且在细菌感染和炎症反应的控制中起重要作用。该文将讨论NLRs在炎症疾病中的调控作用。     

Modulation of the NOD-like receptors NOD1 and NOD2: A chemist’s perspective

The innate immune system is the body’s first defense against invading microorganisms, relying on the recognition of bacterial-derived small molecules by host protein receptors. This recognition event and downstream immune response rely heavily on the specific chemical features of both the innate immune receptors and their bacterial derived ligands. This review presents a chemist’s perspective on some of the most crucial and complex components of two receptors (NOD1 and NOD2): starting from the structural and chemical characteristics of bacterial-derived small molecules, to the specific proposed models of molecular recognition of these molecules by immune receptors, to the subsequent post-translational modifications that ultimately dictate downstream immune signaling. Recent advances in the field are discussed, as well as the potential for the development of targeted therapeutics.     

When Rab GTPases meet innate immune signaling pathways

Ras-related protein in brain (Rab) GTPases, the subfamily of small GTP-binding proteins superfamily, play a vital role in regulating and controlling vesicles' transport between different membrane-bound organelles. As the first-line defense against invading pathogens, the host's innate immune system recognizes various pathogen-associated molecular patterns through a series of membrane-bound or cytoplasmic pathogen recognition receptors to activate the downstream signaling pathway and induce the type I interferons (IFN-I). Numerous studies have demonstrated that Rab GTPases participate in innate immunity by regulating transmembrane signals' transduction and the transport, adhesion, anchoring, and fusion of vesicles. However, the underlying mechanism of Rab GTPases regulating innate immunity is not entirely understood. A comprehensive understanding of the interplay between the Rab GTPases and innate immunity will help develop novel therapeutics against microbial infections and chronic inflammations.