Functional polymorphisms in Toll-like receptor genes for innate immunity in farm animals

Novák, Karel

doi:10.1016/j.vetimm.2013.10.016

Cited by 38 publications

(33 citation statements)

References 85 publications

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“…Innate immunity is the first line of defense against pathogens and body injury, which is triggered by recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) [ 7 ]. PRRs include Nod-like receptors (NLRs), which mediate cytosolic recognition of microbial molecules and promote their clearance [ 7 – 9 ], and Toll-like receptors (TLRs), which are located at the cell surface or within endosomal membranes and recognize a wide range of microbial molecules such as lipopolysaccharide (LPS), peptidoglycan, lipoteichoic acid, flagellin, and zymosan [ 8 , 10 , 11 ]. NOD2 senses muramyl dipeptide (MDP), which is a conserved structure in bacterial peptidoglycan (PGN) [ 12 ].…”

Section: Resultsmentioning

confidence: 99%

Characterization of TLR2, NOD2, and related cytokines in mammary glands infected by Staphylococcus aureus in a rat model

Wang

et al. 2015

Acta Vet Scand

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BackgroundStaphylococcus aureus causes subclinical mastitis as well as persistent and chronic infections in cattle. Bovine mastitis induced by S. aureus is often refractory to antibiotic treatment. Local innate immune defenses play an important role in eliminating the invading bacteria. TLR2 and NOD2 are important pathogen recognition receptors, but their functions have not been investigated in the context of early stages of mastitis. The present study examined TLR2, NOD2, and related cytokines in mammary glands infection induced by S. aureus at early stages in a rat mastitis model.FindingsAll inoculated mammary glands developed mastitis. Acute changes were induced in mammary tissues infected with S. aureus at early stages and then chronic infections persisted until the end of the experiment. TLR2 and NOD2 mRNA expression increased significantly after inoculation with S. aureus. The expression levels of cytokine mRNAs, including TNF-α, IL-1β, IL-6, IL-10, and CXCL1, also increased. TGF-β1 expression was suppressed at early phase and IFN-γ mRNA expression increased significantly at a later stage.ConclusionsMammary innate immune responses were activated after S. aureus inoculation. TLR2, NOD2, and inflammatory cytokines (TNF-α, IL-1β, IL-6, CXCL1, IL-10, TGF-β1, and IFN-γ) are involved in the response to mastitis induced by S. aureus.Electronic supplementary materialThe online version of this article (doi:10.1186/s13028-015-0116-0) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Characterization of TLR2, NOD2, and related cytokines in mammary glands infected by Staphylococcus aureus in a rat model

Wang

et al. 2015

Acta Vet Scand

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“…Differences in expression levels of receptors and proteins involved in pathogen recognition can affect the propensity for an animal to develop an infection (Fonseca et al, 2011;Kandasamy and Kerr, 2012;Novák, 2014). Enhanced pathogen detection, due to genetic or epigenetic differences between animals, could be a major factor differentiating the high versus low phenotype observed in our fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Cow-to-cow variation in fibroblast response to a toll-like receptor 2/6 agonist and its relation to mastitis caused by intramammary challenge with Staphylococcus aureus

Benjamin

Green

Hayden

et al. 2015

Journal of Dairy Science

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Staphylococcus aureus is a common cause of chronic mammary gland infections in dairy cattle. However, the inflammatory response and duration of infection following pathogen exposure is variable between individual animals. To investigate interanimal differences in immune response, dermal fibroblast cultures were established from skin biopsies collected from 50 early lactation Holstein cows. The fibroblasts ability to produce IL-8 in response to a 24-h treatment with a synthetic toll-like receptor 2/6 agonist (Pam2CSK4) was used to assign a response phenotype to the animals. Five high-responding and 5 low-responding animals were then selected for an intramammary challenge with S. aureus to evaluate differences in the inflammatory response, chronicity of infection, and development of antibodies to the pathogen. All animals exhibited clinical symptoms of mastitis at 24h postchallenge. Animals previously classified as high responders experienced a greater inflammatory response characterized by elevated levels of milk somatic cell count, IL-8, and BSA following the challenge compared with low responders. In addition, antibodies toward the challenge strain of S. aureus reached higher levels in whey from the challenged gland of high responders compared with low responders. Despite the antibody response, all 5 high responders were chronically infected for the 6-wk duration of the study, whereas 2 of the low responders cleared the infection, although 1 of these did become reinfected. The observed differences between animals classified as low and high responders based on their fibroblast responsiveness suggests that this cell type can be used to further examine the causes of interanimal variation in response to mammary infection.

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“…118 Alongside these, several other reports have also demonstrated the impact of TLR polymorphisms on the outcomes of diseases in different animal population (as reviewed in Ref. 119 ). Hitherto, most of the studies are aiming towards uncovering the molecular insights related to human.…”

Section: Tlr Polymorphisms In Animal Model Of Infectious Diseasesmentioning

confidence: 91%

Toll‐like receptor polymorphism in host immune response to infectious diseases: A review

2019

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Immunopolymorphism is considered as an important aspect behind the resistance or susceptibility of the host to an infectious disease. Over the years, researchers have explored many genetic factors for their role in immune surveillance against infectious diseases. Polymorphic characters in the gene encoding Toll-like receptors (TLRs) play profound roles in inducing differential immune responses by the host against parasitic infections. Protein(s) encoded by TLR gene(s) are immensely important due to their ability of recognizing different types of pathogen associated molecular patterns (PAMPs). This study reviews the polymorphic residues present in the nucleotide or in the amino acid sequence of TLRs and their influence on alteration of inflammatory signalling pathways promoting either susceptibility or resistance to major infectious diseases, including tuberculosis, leishmaniasis, malaria and filariasis. Population-based studies exploring TLR polymorphisms in humans are primarily emphasized to discuss the association of the polymorphic residues with the occurrence and epidemiology of the mentioned infectious diseases. Principal polymorphic residues in TLRs influencing immunity to infection are mostly single nucleotide polymorphisms (SNPs). are presented as the major influential SNPs in shaping immunity to pathogenic infections. The contribution of these SNPs in the structure-function relationship of TLRs is yet not clear. Therefore, molecular studies on such polymorphisms can improve our understanding on the genetic basis of the immune response and pave the way for therapeutic intervention in a more feasible way.

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Functional polymorphisms in Toll-like receptor genes for innate immunity in farm animals

Cited by 38 publications

References 85 publications

Characterization of TLR2, NOD2, and related cytokines in mammary glands infected by Staphylococcus aureus in a rat model

Characterization of TLR2, NOD2, and related cytokines in mammary glands infected by Staphylococcus aureus in a rat model

Cow-to-cow variation in fibroblast response to a toll-like receptor 2/6 agonist and its relation to mastitis caused by intramammary challenge with Staphylococcus aureus

Toll‐like receptor polymorphism in host immune response to infectious diseases: A review

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