Influence of polymorphisms in porcine NOD2 on ligand recognition

Jozaki, Kosuke; Shinkai, Hiroki; Tanaka-Matsuda, Maiko; Morozumi, Takeya; Matsumoto, Toshimi; Toki, Daisuke; Okumura, Naohiko; Eguchi-Ogawa, Tomoko; Kojima-Shibata, Chihiro; Kadowaki, Hiroshi; Suzuki, Eisaku; Wada, Yasuhiko; Uenishi, Hirohide

doi:10.1016/j.molimm.2009.09.030

Cited by 21 publications

(23 citation statements)

References 21 publications

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“…Thus, TLRs 1–10 have been cloned and sequenced; surface and endosomal TLRs have been detected—both by PCR and immunohistochemistry—in a variety of porcine tissues and enhanced expression demonstrated in response to a number of infectious agents and PAMPs . Members of the NLR family have also been identified and current research suggests that porcine PRR signaling pathways are similar to those of other mammalian species …”

Section: Immunopathology Of Sepsismentioning

confidence: 99%

The Immunopathology of Sepsis: Pathogen Recognition, Systemic Inflammation, the Compensatory Anti‐Inflammatory Response, and Regulatory T Cells

Lewis

Chan

Pinheiro

et al. 2012

Veterinary Internal Medicne

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Sepsis, the systemic inflammatory response to infection, represents the major cause of death in critically ill veterinary patients. Whereas important advances in our understanding of the pathophysiology of this syndrome have been made, much remains to be elucidated. There is general agreement on the key interaction between pathogen‐associated molecular patterns and cells of the innate immune system, and the amplification of the host response generated by pro‐inflammatory cytokines. More recently, the concept of immunoparalysis in sepsis has also been advanced, together with an increasing recognition of the interplay between regulatory T cells and the innate immune response. However, the heterogeneous nature of this syndrome and the difficulty of modeling it in vitro or in vivo has both frustrated the advancement of new therapies and emphasized the continuing importance of patient‐based clinical research in this area of human and veterinary medicine.

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Section: Immunopathology Of Sepsismentioning

confidence: 99%

The Immunopathology of Sepsis: Pathogen Recognition, Systemic Inflammation, the Compensatory Anti‐Inflammatory Response, and Regulatory T Cells

Lewis

Chan

Pinheiro

et al. 2012

Veterinary Internal Medicne

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“…Our explorations of polymorphisms using the cDNA sequences and ESTs presented here have been useful in characterizing the genetic features of pig breeds and populations [18,42]. We have also investigated polymorphisms in genes encoding pattern-recognition receptors [43-46] and have demonstrated that some of the polymorphisms observed so far in commercial pig and wild boar populations truly affect the ligand-recognition ability of the molecules encoded by the genes [47-49]. In addition, many ongoing studies are revealing the potential associations of gene polymorphisms with economically important traits in pigs [50].…”

Section: Resultsmentioning

confidence: 99%

Large-scale sequencing based on full-length-enriched cDNA libraries in pigs: contribution to annotation of the pig genome draft sequence

Uenishi

Morozumi²,

Toki³

et al. 2012

BMC Genomics

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BackgroundAlong with the draft sequencing of the pig genome, which has been completed by an international consortium, collection of the nucleotide sequences of genes expressed in various tissues and determination of entire cDNA sequences are necessary for investigations of gene function. The sequences of expressed genes are also useful for genome annotation, which is important for isolating the genes responsible for particular traits.ResultsWe performed a large-scale expressed sequence tag (EST) analysis in pigs by using 32 full-length-enriched cDNA libraries derived from 28 kinds of tissues and cells, including seven tissues (brain, cerebellum, colon, hypothalamus, inguinal lymph node, ovary, and spleen) derived from pigs that were cloned from a sow subjected to genome sequencing. We obtained more than 330,000 EST reads from the 5′-ends of the cDNA clones. Comparison with human and bovine gene catalogs revealed that the ESTs corresponded to at least 15,000 genes. cDNA clones representing contigs and singlets generated by assembly of the EST reads were subjected to full-length determination of inserts. We have finished sequencing 31,079 cDNA clones corresponding to more than 12,000 genes. Mapping of the sequences of these cDNA clones on the draft sequence of the pig genome has indicated that the clones are derived from about 15,000 independent loci on the pig genome.ConclusionsESTs and cDNA sequences derived from full-length-enriched libraries are valuable for annotation of the draft sequence of the pig genome. This information will also contribute to the exploration of promoter sequences on the genome and to molecular biology-based analyses in pigs.

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“…We found many polymorphisms in the CDSs, particularly in the regions encoding domains required for ligand recognition [4-7]. Many SNPs changing the encoding of amino acids (nonsynonymous SNPs) were included in the ligand-recognizing regions.…”

Section: Resultsmentioning

confidence: 99%

“…Human cells (HEK293) into which expression vectors carrying some of the PRR polymorphisms had been introduced showed varying responses to a ligand. For example, the response of pig NOD2 with a 1949T→C mutation to muramyldipeptide was completely abolished, whereas that of pig NOD2 with 2197A→C showed an increased response to the ligand [4]. Furthermore, we have so far detected several nonsynonymous SNPs in TLR2 , TLR4 , and TLR5 that affected their molecular function in ligand recognition (Shinkai et al, unpublished data).…”

Section: Resultsmentioning

confidence: 99%

“…We used Landrace, Large White, Duroc, Berkshire, Hampshire, Middle Yorkshire, Clawn miniature, Potbelly, Meishan, and Jinhua breed pigs and Japanese Wild boars for polymorphisms detection [4-7]. Pig samples for exploration of polymorphisms were collected as ear notches, semen, peripheral blood, or muscle tissues, and genomic DNA was extracted by a standard method.…”

Section: Methodsmentioning

confidence: 99%

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Polymorphisms in pattern recognition receptors and their relationship to infectious disease susceptibility in pigs

Uenishi

Shinkai

Morozumi³

et al. 2011

BMC Proc

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BackgroundPattern recognition receptors (PRRs), including Toll-like receptors (TLRs), are censoring receptors for molecules derived from bacteria, viruses, and fungi. The PRR system is a prerequisite for proper responses to pathogens, for example by cytokine production, resulting in pathogen eradication. Many cases of polymorphisms in PRR genes affecting the immune response and disease susceptibility are known in humans and mice.MethodsWe surveyed polymorphisms in pig genes encoding PRRs and investigated the relationship between some of the detected polymorphisms and molecular function or disease onset.ResultsNonsynonymous polymorphisms abounded in pig TLR genes, particularly in the region corresponding to the ectodomains of TLRs expressed on the cell surface. Intracellular TLRs such as TLR3, TLR7, and TLR8, and other intracellular PRRs, such as the peptidoglycan receptor NOD2 and viral RNA receptors RIG-I and MDA5, also possessed nonsynonymous polymorphisms. Several of the polymorphisms influenced molecular functions such as ligand recognition. Polymorphisms in the PRR genes may be related to disease susceptibility in pigs: pigs with a particular allele of TLR2 showed an increased tendency to contract pneumonia.ConclusionsWe propose the possibility of pig breeding aimed at disease resistance by the selection of PRR gene alleles that affect pathogen recognition.

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Influence of polymorphisms in porcine NOD2 on ligand recognition

Cited by 21 publications

References 21 publications

The Immunopathology of Sepsis: Pathogen Recognition, Systemic Inflammation, the Compensatory Anti‐Inflammatory Response, and Regulatory T Cells

The Immunopathology of Sepsis: Pathogen Recognition, Systemic Inflammation, the Compensatory Anti‐Inflammatory Response, and Regulatory T Cells

Large-scale sequencing based on full-length-enriched cDNA libraries in pigs: contribution to annotation of the pig genome draft sequence

Polymorphisms in pattern recognition receptors and their relationship to infectious disease susceptibility in pigs

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