Novel mutations in TLR genes cause hyporesponsiveness to Mycobacterium avium subsp. paratuberculosis infection

Bhide, Mangesh; Mucha, Rastislav; Mikula, I.; Kisova, L.; Škrabana, Rostislav; Novák, Michal

doi:10.1186/1471-2156-10-21

Cited by 47 publications

(62 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Kb = kilobase. k Bovine health-related QTL overlapping or proximal to investigated gene (Q), or intragenic variation associated (A) with disease susceptibility in case-control studies (25)(26)(27)(28)(29)(30)(31). l Average across all investigated genes.…”

Section: Resultsmentioning

confidence: 99%

“…Validated polymorphisms, haplotype distributions, and tagSNPs/Indels elucidated in this study will directly facilitate fine mapping of existing bovine healthrelated QTL while also enabling independent evaluation of SNPs tentatively associated with susceptibility to Johne disease (25)(26)(27)(28)(29)(30)(31). Because of limitations related to our genotyping assays, we were able to technically ascertain all previously described coding polymorphisms (27)(28)(29)33) only for bovine TLR10, and TLR1 variants posed the greatest technical challenge because of sequence similarity with TLR6.…”

Section: Discussionmentioning

confidence: 99%

“…Our analysis of haplotype structure, LD architecture, and tagSNP/ Indel assignment for 11 bovine innate immune genes will enable studies which assess the relationships between variation within these genes and differential susceptibility to disease (25)(26)(27)(28)(29)(30)(31). Moreover, our analyses will contribute to the design of next-generation bovine genotyping assays for mapping variation underlying bovine health-related traits.…”

Section: Discussionmentioning

confidence: 99%

“…To date, several studies have demonstrated that some naturally occurring TLR variants enhance the risk of severe infections in humans, mice, and most recently, domestic cattle (23)(24)(25)(26). In addition to the emerging molecular and population-based casecontrol data, bovine health-related quantitative trait loci (QTL) have been localized to genomic regions either proximal to or directly overlapping one or more TLR loci, and at least two healthrelated QTL are proximal to PGLYRP1 (25)(26)(27)(28)(29)(30)(31).…”

mentioning

confidence: 99%

“…In addition to the emerging molecular and population-based casecontrol data, bovine health-related quantitative trait loci (QTL) have been localized to genomic regions either proximal to or directly overlapping one or more TLR loci, and at least two healthrelated QTL are proximal to PGLYRP1 (25)(26)(27)(28)(29)(30)(31). Unfortunately, the resolution of the highest density SNP assay available for cattle, the Illumina BovineSNP50 (32), is inadequate to resolve the identity of any of the TLRs as underlying these QTL.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Diversity and evolution of 11 innate immune genes in Bos taurus taurus and Bos taurus indicus cattle

Seabury

Seabury²,

Decker³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

100

View full text Add to dashboard Cite

The Toll-like receptor (TLR) and peptidoglycan recognition protein 1 (PGLYRP1) genes play key roles in the innate immune systems of mammals. While the TLRs recognize a variety of invading pathogens and induce innate immune responses, PGLYRP1 is directly microbicidal. We used custom allele-specific assays to genotype and validate 220 diallelic variants, including 54 nonsynonymous SNPs in 11 bovine innate immune genes (TLR1-TLR10, PGLYRP1) for 37 cattle breeds. Bayesian haplotype reconstructions and median joining networks revealed haplotype sharing between Bos taurus taurus and Bos taurus indicus breeds at every locus, and we were unable to differentiate between the specialized B. t. taurus beef and dairy breeds, despite an average polymorphism density of one locus per 219 bp. Ninety-nine tagSNPs and one tag insertion-deletion polymorphism were sufficient to predict 100% of the variation at all 11 innate immune loci in both subspecies and their hybrids, whereas 58 tagSNPs captured 100% of the variation at 172 loci in B. t. taurus. PolyPhen and SIFT analyses of nonsynonymous SNPs encoding amino acid replacements indicated that the majority of these substitutions were benign, but up to 31% were expected to potentially impact protein function. Several diversitybased tests provided support for strong purifying selection acting on TLR10 in B. t. taurus cattle. These results will broadly impact efforts related to bovine translational genomics.peptidoglycan recognition protein | bovine translational genomics | bovine Toll-like receptors | single nucleotide polymorphism

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Diversity and evolution of 11 innate immune genes in Bos taurus taurus and Bos taurus indicus cattle

Seabury

Seabury²,

Decker³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

100

View full text Add to dashboard Cite

show abstract

Cell-Specific Expression Pattern of Toll-Like Receptors and Their Roles in Animal Reproduction

Atlı

Hitit

Özbek

et al. 2022

Toll-Like Receptors in Health and Disease

View full text Add to dashboard Cite

TLR4, IL10RA, and NOD2 mutation in paediatric Crohn’s disease patients: an association with Mycobacterium avium subspecies paratuberculosis and TLR4 and IL10RA expression

Wagner

Skinner

Catto‐Smith

et al. 2013

Med Microbiol Immunol

View full text Add to dashboard Cite

Mycobacterium avium subspecies paratuberculosis (MAP) has been implicated in the pathogenesis of Crohn's disease (CD). The role of CD susceptibility genes in association with these microbes is not known. Sixty-two early onset paediatric CD patients and 46 controls with known MAP status were analysed for an association with 34 single nucleotide polymorphisms (SNPs) from 18 CD susceptibility genes. Functional studies on peripheral blood mononuclear cells (PBMCs) were conducted on 17 CD patients with known CD mutations to assess IL-6, IL-10, and TNF-α expression upon stimulation with MAP precipitated protein derivative (PPD) and lipopolysaccharide (LPS). In addition, surface expression of IL10R and TLR4 on resting B cells, NK cells, T cells, and monocytes was assessed. A mutation in TLR4 (rs4986790) and IL10RA (rs22291130) was significantly associated with MAP-positive CD patients compared to MAP-negative CD patients (27.6 vs. 6.1 %, p = 0.021, and 62.1 vs. 33.3 %, p = 0.024, respectively). PPD and LPS significantly increased IL-6, IL-10, and TNF-α production in PBMCs. IL-10 and TNF-α production were significantly lower in a subgroup of CD patients (5/12) with a known NOD2 mutation. Receptor for IL-10 was significantly higher expressed on NK cells (CD56low) and on NK T cells harbouring a NOD2 mutations compared to wildtype cells (p = 0.031 and 0.005, respectively). TLR4 was significantly higher expressed on NK cells (CD56high) harbouring a NOD2 mutations compared to wildtype cells (p = 0.038).

show abstract

Novel mutations in TLR genes cause hyporesponsiveness to Mycobacterium avium subsp. paratuberculosis infection

Abstract: Background: Toll like receptors (TLR) play the central role in the recognition of pathogen associated molecular patterns (PAMPs). Mutations in the TLR1, TLR2 and TLR4 genes may change the ability to recognize PAMPs and cause altered responsiveness to the bacterial pathogens.

Cited by 47 publications

References 67 publications

Diversity and evolution of 11 innate immune genes in Bos taurus taurus and Bos taurus indicus cattle

Diversity and evolution of 11 innate immune genes in Bos taurus taurus and Bos taurus indicus cattle

Cell-Specific Expression Pattern of Toll-Like Receptors and Their Roles in Animal Reproduction

TLR4, IL10RA, and NOD2 mutation in paediatric Crohn’s disease patients: an association with Mycobacterium avium subspecies paratuberculosis and TLR4 and IL10RA expression

Contact Info

Product

Resources

About