Leucine-rich repeats and pathogen recognition in Toll-like receptors

Bell, Jessica K.; Mullen, Gregory; Leifer, Cynthia A.; Mazzoni, Alessandra; Davies, David R.; Segal, David M.

doi:10.1016/s1471-4906(03)00242-4

Cited by 680 publications

(532 citation statements)

References 33 publications

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“…Analyzed with the SMART program, GrTLR3 was seen to contain 14 LRRs, which is similar to the observations in zebrafish (15) and in human (18), although 23 LRRs were reported in human TLR3 by Bell et al (2003). The discrepancy might be due to the different programs used to identify the repeats.…”

Section: Discussionsupporting

confidence: 79%

Toll-like receptor 3 regulates Mx expression in rare minnow Gobiocypris rarus after viral infection

Zhang

Wang

et al. 2008

Immunogenetics

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Toll-like receptor 3 (TLR3) plays a key role in activating immune responses during viral infection. To study the genes involved in the regulatory function of TLR3 in the rare minnow Gobiocypris rarus after viral infection, a full-length cDNA of TLR3 (GrTLR3) with a splice variant (GrTLR3s) was identified by homologous cloning and RACE techniques. The antiviral effector molecule Mx gene was cloned and partially sequenced. The mRNA expression levels of GrTLR3, GrTLR3s, and Mx were studied in different tissues before and after virus infection by real-time quantitative RT-PCR. The transcripts of all three genes in liver were significantly increased following GCRV infection (P<0.05). The mRNA levels in liver were upregulated at 24 h post-injection for GrTLR3 and GrTLR3s, and at 12 h for Mx. The upregulated expression levels were several folds for GrTLR3s, tens of folds for GrTLR3, and hundreds of folds for Mx. By semiquantitative RT-PCR, GrTLR3 and Mx expressed at all the developmental stages, whereas GrTLR3s could only be detected at later developmental stages. Using RNAi and transgenic techniques, GrTLR3 mediated Mx expression but GrTLR3s did not. The time-dependent upregulation of receptor and effector, and the Mx over-expression dependent on TLR3, indicated that GrTLR3 regulated Mx expression in viral infection through a configuration change in rare minnow, and its splice variant did not contribute to the process.

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Section: Discussionsupporting

confidence: 79%

Toll-like receptor 3 regulates Mx expression in rare minnow Gobiocypris rarus after viral infection

Zhang

Wang

et al. 2008

Immunogenetics

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“…In either case, the NITRs present a compelling case for parallel evolution of BCR-and TCR-type V-region diversity in the context of innate immunity. [94][95][96][97][98] . The LRR-encoding cDNAs in lampreys are encoded at a single locus.…”

Section: Nk and Nk-type Receptors In Jawed Vertebratesmentioning

confidence: 99%

Section: Anticipatory Immunity In Jawless Vertebratesmentioning

confidence: 99%

“…Subtracted cDNAs recovered from these cell cultures are highly enriched in sequences encoding a particularly complex set of LEUCINE-RICH REPEAT (LRR)-containing extracellular molecules. Notably, LRRs are a core feature of markedly diverse forms of pattern-recognition molecule that mediate receptor-ligand interactions throughout phylo geny [94][95][96][97][98] . The LRR-encoding cDNAs in lampreys are encoded at a single locus.…”

Section: Anticipatory Immunity In Jawless Vertebratesmentioning

confidence: 99%

“…The postulated role of the VLRs as alternative mediators of adaptive immunity might have an even more ancient history within the broader functional roles of other metazoan LRRcontaining proteins, which include the Toll-like receptor (TLR) 94 , CATERPILLER (caspase-recruitment domain, transcription enhancer, R (purine)-binding, pyrin, lots of LRRs) 100 and Slit-homologue protein families 101,102 . The TLRs have particularly broad distributions in phylogeny and are closely involved in mammalian immune surveillance [103][104][105] .…”

Section: Anticipatory Immunity In Jawless Vertebratesmentioning

confidence: 99%

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Reconstructing immune phylogeny: new perspectives

2005

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Numerous studies of the mammalian immune system have begun to uncover profound interrelationships, as well as fundamental differences, between the adaptive and innate systems of immune recognition. Coincident with these investigations, the increasing experimental accessibility of non-mammalian jawed vertebrates, jawless vertebrates, protochordates and invertebrates has provided intriguing new information regarding the likely patterns of emergence of immune-related molecules during metazoan phylogeny, as well as the evolution of alternative mechanisms for receptor diversification. Such findings blur traditional distinctions between adaptive and innate immunity and emphasize that, throughout evolution, the immune system has used a remarkably extensive variety of solutions to meet fundamentally similar requirements for host protection.The evolutionary development of the METAZOANS was associated with the diversification of a wide range of specialized cell-surface molecules that mediate key metabolic processes, as well as provide crucial contact interfaces and carry out a broad range of other essential functions. It is not unexpected that some of these molecules also came to function as barriers to pathogenic invasion and, in doing so, began to carry out dedicated innate immune protective functions. Whereas the simplest form of protection, barrier formation, is essentially mechanical in nature, relentless pressure from genetic variation in pathogens probably drove the evolution of such innate immune protective molecules towards diversification and, in parallel, towards integration of signalling pathways to regulate cellular responses to external stimulation. However, despite the sophistication that such innate immune mediators achieved over time, their biological complexity, by definition, would be limited by genome space, so with increasing complexity of body plan and/or increasing pathogen sophistication, they could be overwhelmed. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptMore than 500 million years ago, a TRANSPOSITION event, probably involving a recombinationactivating gene (RAG)-bearing element, might have given rise to the predecessors of the rearranging antigen-binding receptors of the jawed vertebrates, which encompass the vertebrate radiations that extend from the cartilaginous fish through to humans. This is considered the defining point in the emergence of RAG-mediated (conventional) adaptive immunity 1,2 , which has evolved to create a mechanism for deriving almost limitless variation from very few genes. Studies in traditional and non-traditional animal models, such as sharks, bony fish and birds, have brought this event and its ramifications for host defence into sharper focus. We can now predict much about how these rearranging antigenbinding receptors probably arose, what alternative pathways of immune-receptor gene evolution have occurred, what relationships exist between B-and T-cell-mediated immunity and natural killer (NK)-cell function, how complex immune ...

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Toward a structural understanding of nucleic acid‐sensing Toll‐like receptors in the innate immune system

2017

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The history of mankind has been plagued by the tug of war with viral infections. Toll-like receptors (TLRs) and other receptors of the innate immune system constitute an early defense system against invading viruses by recognizing the viral genetic material, the nucleic acids (NAs). Agonistic ligands of NA-sensing TLRs play an emerging role in the treatment of viral diseases, demonstrating a crucial role of these receptors. Recently, crystal structures have afforded new insights into TLR recognition of NAs. An aberrant activation by self-NAs, which leads to the inflammation and autoimmunity, is avoided by strict regulation of NA-TLR interaction at multiple check-points. This Review summarizes the novel structural understanding of NA-sensing by TLRs and regulatory mechanisms of these receptors.

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Leucine-rich repeats and pathogen recognition in Toll-like receptors

Cited by 680 publications

References 33 publications

Toll-like receptor 3 regulates Mx expression in rare minnow Gobiocypris rarus after viral infection

Toll-like receptor 3 regulates Mx expression in rare minnow Gobiocypris rarus after viral infection

Reconstructing immune phylogeny: new perspectives

Toward a structural understanding of nucleic acid‐sensing Toll‐like receptors in the innate immune system

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