Toll-like Receptor 4 Gene Research Articles

Physical Activity Maintain Immune Response Through TLR-2/TLR-4 Gene Expression in Type-2 Diabetes Mellitus Patient at Medan City.

The Increasing in type-2 diabetes mellitus (T2DM) needs to solve comprehensively and holistically. Patients with T2DM should have self-coping due to lifestyle modification. Abdominal fat accumulation can release pro-inflammatory cytokine that leads TLR-2 and TLR-4 to the response. These two kinds of toll-like receptors exist on the monocyte surface membrane which is an innate immunity cell. The aims of this study were to get the profile of physical activity, metabolic state, and mononuclear cell response to the expression of the TLR2 and TLR4 genes in T2DM patients. It was a descriptive-analytic study with a cross-sectional study design. Thirty-two eligible patients with inclusion criteria participated as subjects. All subjects answered questions by IPAQ, and checked metabolic state with body composition analysis. The TLR2 and TLR4 gene expression was determined with quantitative Real- Time PCR. This study result found that most T2DM patients were in a highly active category in which most of their activity was walking (light intensity). The average abdominal circumferences were 91.81 ± 15.4 cm, body fat percentage was 29.5 ± 8.8%, and fasting blood sugar was 187.07 ± 67.03 mg/dl. Mononuclear cells number were normal. The expression of the TLR2 gene was lower by 0.71 fold and TLR4 gene expression was lower by 0.9 fold compared with non-DM (p<0.05). By chi-square test, there was a positive correlation between TLR2 gene expression with fasting blood glucose (p=0.011, and a positive correlation between the abdominal circumference and TLR4 gene expression (p=0.011). Type-2 Diabetes mellitus patients in primary health care keep walking as their physical activity to maintain blood glucose. Patients need to do moderate to vigorous exercise regularly to reduce body fat percentage especially abdominal fat to reduce Toll-like receptor gene expression, so insulin resistance and blood glucose level might decline to normal.

Silencing TLR4 using an ultrasound-targeted microbubble destruction-based shRNA system reduces ischemia-induced seizures in hyperglycemic rats.

The toll-like receptor 4 (TLR4) pathway is involved in seizures. We investigated whether ultrasound-targeted microbubble destruction (UTMD)-mediated delivery of short hairpin RNA (shRNA) targeting the TLR4 gene (shRNA-TLR4) can reduce ischemia-induced seizures in rats with hyperglycemia. A total of 100 male Wistar rats were randomly assigned to five groups: (1) Sham; (2) normal saline (NS); (3) shRNA-TLR4, where rats were injected with shRNA-TLR4; (4) shRNA-TLR4 + US, where rats were injected with shRNA-TLR4 followed by ultrasound (US) irradiation; and (5) shRNA-TLR4 + microbubbles (MBs) + US, where rats were injected with shRNA-TLR4 mixed with MBs followed by US irradiation. Western blot and immunohistochemical staining were used to measure TLR4-positive cells. Half of the rats in the NS group developed tonic-clonic seizures, and TLR4 expression in the CA3 region of the hippocampus was increased in these rats. In addition, the NS group showed an increased number of TLR4-positive cells compared with the Sham group, while there was a decreased number of TLR4-positive cells in the shRNA, shRNA + US, and shRNA + MBs + US groups. Our findings indicate that the TLR4 pathway is involved in the pathogenesis of ischemia-induced seizures in hyperglycemic rats and that UTMD technology may be a promising strategy to treat brain diseases.

Effects of carbamazepine on gut microbiota, ARGs and intestinal health in zebrafish

Carbamazepine (CBZ) in the aquatic environment is recognized as a potential threat to aquatic organisms and public health. However, the response of organism intestinal health, resistome, microbiota, and their relationship after CBZ exposure has been rarely reported. This study aimed to explore the impacts of CBZ on gut microbiota, antibiotic resistance genes (ARGs) and the expression of intestinal health related genes as well as their interaction using the zebrafish model. 16 S ribosomal RNA sequencing indicated CBZ altered the composition of gut microbiota. Using high-throughput quantitative polymerase chain reaction (HT-qPCR), we found the number and abundance of ARGs were impacted by CBZ levels and exposure duration. We also observed the upregulated expression of the pro-inflammatory gene IL6 and downregulated expression of toll-like receptor gene TLR2 and intestinal barrier gene TJP2a at different exposure times. Correlation analyses revealed that Geobacillus, Rhodococcus, Ralstonia, Delftia, Luteolibacter and Escherichia-Shigella might be the main bacterial genera carrying ARGs. Meanwhile, Cetobacterium and Aeromonas could be the dominant bacteria affecting intestinal health related genes. Our results could contribute to understanding the health risks of CBZ to the intestinal microecology of aquatic animals.

Molecular Characterization and Gene Expression Of TLR4 Gene Associated with Mastitis in Goats

In this study characterization of Toll-like receptor 4 (TLR4) gene of goats; detection of polymorphisms in the nucleotides, and determination of the association of identified genotypes with the occurrence of subclinical mastitis was done using chi-square and odds ratio. Analyzing gene expression using two-sided Student's T-test was also done. Results of Study 1 revealed high similarity (99%) of TLR4 nucleotide sequence of all breeds of goats with that of C. hircus (NM_001285574.1) and sheep (Ovis aries) sequences and slightly lower similarity with cattle (Bos taurus, and Bos indicus) (96%), and water buffalo (Bubalus bubalis) (95%). In Study 2, restriction fragment length polymorphism (RFLP) analysis revealed three genotypes with nine restriction patterns using AluI enzyme. Genotype AA has odds ratio of 0.28 and 0.08 in all breeds, and in Anglo-Nubian, respectively, with significant association (P0.05) that inferred 0.28 and 0.08 times greater probability in all breeds, and in Anglo-Nubian, respectively, for subclinical mastitis to occur than those of other genotypes. Genotype AB showed odds ratio of 3.83, 13.00 and 2.40 in all breeds, in Anglo-Nubian, and in Upgraded, respectively, with significant association (P0.05) that indicated 3.83, 13.00 and 2.40 times more likely in all breeds, in Anglo-Nubian, and in Upgraded, respectively, to suffer subclinical mastitis than those of other genotypes. Â In Study 3, genetic expression analysis showed a significant upregulation of TLR4 gene up to maximum of 3.63-fold in goats without subclinical mastitis compared to subclinically mastitic animals with only 0.65-fold which suggest a prompt role of TLR4 gene in the protection of animal against possible infection.Â

Bifidobacterium longum, Lactobacillus plantarum and Pediococcus acidilactici Reversed ETEC-Inducing Intestinal Inflammation in Mice.

Microecological preparation could relieve Enterotoxigenic Escherichia coli (ETEC) K88-induced diarrhea in piglets, but which bacteria play a key role and the mitigation mechanism have not been fully clarified. In this study, 36 male mice were randomly divided into six groups (CON, K88, BK (Bifidobacterium longum + K88), LK (Lactobacillus plantarum + K88), PK (Pediococcus acidilactici + K88), and MK (mixed strains + K88)) to explore the prevention mechanisms. Three probiotic strains and their mixtures (TPSM) significantly relieved the weight loss and restored the ratio of villus height to crypt depth in the jejunum. Except for Bifidobacterium longum, other strains significantly decreased interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in mice serum. The TPSM treatment significantly downregulated the mRNA expression of the inflammatory cytokines and the Toll-like receptor and downstream gene (TLR4, MyD88, NF-κB) in jejunum induced by ETEC. Furthermore, the TPSM could restore dysbiosis of the intestinal microbiota caused by ETEC. The intestinal microbiota analysis demonstrated that Bifidobacterium longum enriched the Bifidobacterium genus (p < 0.05), Lactobacillus plantarum enriched the Lactobacillus genus (p < 0.05), Pediococcus acidilactici enriched the Coriobacteriaceae_UCG-002 and Christensenellaceae_R-7_group genus (p < 0.05), mixed bacteria enriched the Akkermansia genus (p < 0.05), but ETEC enriched the Desulfovibrio genus (p < 0.05). Meanwhile, the starch and sucrose metabolism, galactose and fructose metabolism, mannose metabolism and ABC transporters were increased with probiotics pre-treatment (p < 0.05). To sum up, the microecological preparation alleviated ETEC-induced diarrhea by regulating the immune response, rebalancing intestinal microbiota and improving carbohydrate metabolism.

Evolutionary Impacts of Pattern Recognition Receptor Genes on Carnivora Complex Habitat Stress Adaptation.

Many mammals develop specific immune responses owing to the changes in their ecological niche and diet that are essential for animal survival. However, pattern recognition receptors (PRRs) serve as the first line of defense in innate immunity and generate immune responses in the host. However, the evolutionary impacts on PRR genes in Carnivora are not well studied. Herein, we explored the evolution of 946 PRR gene sequences in 43 Carnivora species to elucidate the molecular mechanisms of carnivore adaptation to complex habitats. We found that the PRRs were relatively conserved, and different gene families showed different evolutionary patterns. PRRs were highly purified based on their overall roles in Carnivora species but interspersed with positive-selection patterns during evolution. Different niche types may have jointly driven the evolution of PRR genes. In particular, the selection pressure of toll-like receptor (TLR) 10 was relaxed in seven species with pseudogenes, which may have emerged during recent evolutionary events. We speculated that a "functional compensation" mechanism may exist for genes with overlapping functions in the TLR gene family. Additionally, TLR2, TLR4, NLRC5, and DECTIN1 were subject to positive selection in semi-aquatic species, and the adaptive evolution of these genes may have been related to the adaptation to semi-aquatic environments. In summary, our findings offer valuable insights into the molecular and functional evolution of PRR genes, which are important for immune adaptations in Carnivora.

Genome-wide investigation and expression analysis of TLR gene family reveals its immune role in Vibrio tolerance challenge of Manila clam

Toll-like receptors (TLRs) play key roles in activating immune responses during infection. In this study, we identified TLR genes in Manila clam at the genome-wide level and characterized it into 9 types according to the Ruditapes philippinarum genome annotation, including TLR1 (1–10), TLR2 (1–10), TLR2–2 (1–5), TLR3 (1–3), TLR4 (1–9), TLR5, TLR6 (1–5), TLR7 (1–2), and TLR13 (1–4). The length of TLR proteins varied from 128 to 1257 amino acids. The molecular weights and theoretical isoelectric point (pI) values ranged from 14.63 to 143.32 kDa and 4.47 to 9.45, respectively. TLR genes showed universal expression levels in adductor muscle (AM), mantle (M), foot (F), gill (GI), pipe (P), digestive gland (DG), gonad (GO) and labial palp (L). Transcriptome analysis revealed that the expression level of TLR4, TLR5, TLR7 and TLR13 genes are significantly highly expressed in resistant individuals of Manila clam under Vibrio anguillarum challenge, indicating these TLR genes may play significant roles in response to invading pathogens. The results obtained in this work will provide valuable insights into the immune function of TLR gene in R. philippinarum.

Effects of fumonisin and Salmonella infection in the expression of Toll-like receptors in chicken ovary

Mycotoxins are secondary metabolites produced mainly by fungi that contaminate animal feed and basic food products throughout the world. Currently, more than 500 mycotoxins are reported and one of the most important concern to public health and agriculture is Fumonisin B1 (FB1). FB1, a mycotoxin produced by Fusarium moniliforme, is a contaminant of animal feed with various and complex cellular effects. Although FB1 has been associated with various diseases in animals, to date few studies have been performed to evaluate the endocrine disrupting effects of FB1 and more particularly the effects in the innate immune mechanisms of farm animals and more specifically in poultry species. As the family of Toll-like receptors (TLRs) is one of the key molecules of the innate immune system, the aim of the present study was to evaluate the transcriptional changes of TLRs in the chicken ovary in vivo, in chicks fed with FB1 and in response to Salmonella Enteritidis (SE) infection. RNA was extracted from the ovaries of sexually mature and aged birds, treated with FB1 and SE. Quantitative real-time PCR analysis revealed that FB1 and SE infection resulted in a significant down regulation of 5 TLR genes in the ovary of sexual mature and aged birds. These findings suggest that the mycotoxin FB1 suppresses the innate immune system of the chicken reproductive organs, through alteration in the expression of certain TLR genes.

Genetic variation in toll-like receptor 4 gene with primary antiphospholipid syndrome susceptibility: a cohort of Egyptian patients

BackgroundAs toll-like receptor 4 (TLR4) plays important roles in cellular immunity and TLR4 polymorphisms have been shown to be associated with susceptibility to a range of diseases, the present study aimed to investigate the association between TLR4 gene polymorphisms and the incidence of primary antiphospholipid syndrome (PAPS).MethodsTwo TLR4 single nucleotide polymorphisms (rs4986790 and rs4986791) were assessed in 110 subjects of Egyptian ethnicity, including 65 female patients with PAPS and 45 matched healthy controls, using polymerase chain reaction-restriction fragment length polymorphism. Results were verified using automated sequencing.ResultsThe homozygous wild-type (AA, aspartic acid) rs4986790 variant and (CC, threonine) rs4986791 variant were the predominant genotypes in the control and PAPS groups.ConclusionThe results of this preliminary study of TLR4 gene variants among patients with PAPS in an Egyptian population found no association between the rs4986790 and rs4986791 variants and susceptibility to PAPS.

Genome-wide investigation of toll-like receptor genes (TLRs) in Procambarus clarkia and their expression pattern in response to black may disease

As a crucial component of pattern-recognition receptors (PRRs) that recognizing pathogen-associated molecular patterns (PAMPs) and defending against invading pathogens, the Toll-like receptors (TLRs) have been paid extensive attention. While the identification and functional roles of TLRs in innate immunity have been reported in a plenty of organisms, the systematic knowledge of TLRs is still lacking in the red swamp crayfish (Procambarus clarkia). In current study, a total of 7 tlr genes were identified in P. clarkia based on the published transcriptome and genome data. The PcTLRs length varied from 939 to 1517aa and contain typical domains of TLR protein, including transmembrane region, varied LRR and TIR domains. 7 Pctlr genes were distributed in 5 chromosomes and 2 scaffolds. The expression pattern of different Pctlr genes in different tissues (hepatopancreas, gill and muscle) and in response to black may disease (BMD) showed significant difference. In addition, 5 proteins that might interact with PcTLR-2 were predicted, among them the expression pattern of dorsal and relish was consistent with Pctlr-2 in three tissues, while the other genes were not. The PcTLR-2-Dorsal/Relish pathway might play crucial roles in response to BMD infection. The results provided a theoretical foundation for further studies on the molecular mechanisms of TLRs in BMD infection in the red swamp crayfish and provided reference for the research of other crustacean species.

The beneficial effects of Lacticaseibacillus casei on the small intestine and colon of Swiss mice against the deleterious effects of 5-fluorouracil.

Intestinal mucositis is one of the most common and important side effects of 5-fluorouracil (5-FU). Currently, there are still no specific and effective protocols for its prevention and treatment. The aim of the present study was to evaluate the effect of oral administration of Lacticaseibacillus casei (L. casei) on the progression of 5-FU-induced intestinal mucositis. Methods: L. casei (1x109 CFU/ml) or saline was orally administered to Swiss mice, beginning 15 days before intestinal mucositis induction by single intraperitoneal 5-FU administration (450 mg/kg). Body weight, number of peripheral leukocytes and fecal lactic acid bacteria were monitored. After euthanasia, on day 18, tissue samples from colon and each small intestine segment were collected for histopathology. Jejunal tissues were collected and evaluated for iNOS and TNF-alpha immunoexpression, IL-1-beta, IL-6 and TNF-alpha levels, malonaldehyde (MDA) accumulation, invertase activity and factor nuclear kappa B (NFkB-P65) gene expression, toll like receptor-4 (TLR-4), mucin-2 (MUC-2), occludin and zonula occludens-1 (ZO-1). The positive impact of L. casei on 5-FU-induced leukopenia was observed, but not on 5-FU-induced weight loss in mice. L. casei reduced 5-FU-induced inflammation in the colon and small intestine (p<0.05). Decreased TNF-α, IL-1β, IL-6 (p<0.05) and MDA (p<0.05) levels, as well as decreased iNOS and TNF-alpha protein expressions (p<0.05) were found in the jejunum from L casei group. In addition, L-casei down-regulated NFKB-P65 (p<0.05) and TLR-4 (p<0.05) gene expressions and up-regulated MUC-2 and mucosal barrier proteins occludin and ZO-1 gene expressions (p<0.05). Furthermore, greater lactic acid bacteria population (p<0.05) was found in the L. casei group when compared to control groups. Oral L. casei administration can protect the intestine of Swiss mice from 5-FU-induced intestinal mucositis, thus contributing to overall health.

Molecular cloning, characterization and constitutive expression analysis of TLR4 gene in Pangasianodon hypophthalmus

Toll like receptor (TLR) signalling pathway plays a central role in inflammatory responses through the recognition of PAMPs and DAMPs. Toll-like receptor 4 (TLR4) is well known for the recognition of LPS of gram-negative bacteria leading to production of inflammatory cytokines. Modulation of a TLR pathway gene in different tissues indicates the functional importance of the tissues in innate immunity. The aim of this study was to clone and characterize TLR4 and evaluate its constitutive tissue distribution in Pangasianodon hypophthalmus, a commercially important fish species. The study was carried out at ICAR-CIFE, Mumbai during 2017. Partial nucleotide and amino acid sequences of TLR4 were identified in P. hypophthalmus and termed as phTLR4. Bio-informatics analysis of partial sequence revealed four putative LRR domains characteristic of TLRs. Nucleotide and amino acid sequences showed varying degree of identity with TLR4 sequences from other fish species in BLASTn and BLASTp analysis. Phylogenetic analysis placed the phTLR4 close to Ictalurus punctatus. TLR4 was found to be constitutively expressed in all the tissues studied. The significantly highest expression was recorded in intestine and spleen. The lowest expression was in muscle, heart and skin. House-keeping gene ß-actin was used as an internal control. The outcome of this research will be helpful for studying mRNA expression levels of phTLR4 under different conditions in different tissues of Pangasianodon hypophthalmus.

Genome-Wide Identification, Characterization and Expression Analysis of Toll-like Receptors in Marbled Rockfish (Sebastiscus marmoratus).

Toll-like receptor (TLR) is a cluster of type I transmembrane proteins that plays a role in innate immunity. Based on the marbled rockfish (Sebastiscus marmoratus) genome database, this study used bioinformatics methods to identify and analyze its TLR gene family members. The results showed that there were 11 TLR gene family members in Sebastiscus marmoratus (SmaTLR), which could be divided into five different subfamilies. The number of amino acids encoded by the Smatlr genes ranged from 637 to 1206. The physicochemical properties of the encoded proteins of different members were also computed. The results of protein structure prediction, phylogenetic relation, and motif analysis showed that the structure and function of the SmaTLRs were relatively conserved. Quantitative Real-Time PCR (qRT-PCR) analysis revealed the expression patterns of SmaTLRs in the gill, liver, spleen, head kidney, kidney, and intestine. SmaTLRs were widely detected in the tested tissues, and they tended to be expressed higher in immune-related tissues. After polyriboinosinic polyribocytidylic acid (poly(I:C)) challenge, SmaTLR14, SmaTLR3, SmaTLR5S, SmaTLR7, and SmaTLR22 were significantly upregulated in the spleen or liver. The results of this study will help to understand the status of TLR gene family members of marbled rockfish and provide a basis for further study of the functional analysis of this gene family.

Prediction of deleterious non-synonymous SNPs of human TLR2 gene associated with bacterial meningitis and hearing impairment by computational approach

Background: Bacterial meningitis is the most serious infection of the central nervous system and often occurs in children under the age of 5 years and leads to hearing loss, learning disabilities. Several studies have reported the genetic variation in a gene that is involved in the innate immune system and affects the susceptibility, severity of bacterial infection during meningitis. Methodology: Hence the present study was performed to insights the single nucleotide polymorphisms in pathogen recognition genes especially those that play an essential role in the innate immune system. Toll-like receptor 2 (TLR2) was selected to analyze the association of TLR2 in bacterial meningitis. The coding and non-coding SNPs of the human TLR2 gene was retrieved from the NCBI database and were subjected to various computational prediction tools including SIFT, PolyPhen-2, Imutnat, to predict the high-risk deleterious SNPs and the effect of single amino acid substitutions and structural and functional impact of these mutations was predicted with project HOPE, SNP-GO tools. Results: The result revealed that among the 501 non-synonymous, 9 deleterious SNPs were sorted by SFIT, Polyphen-2 and I mutant serve with SFIT score, DDG score, and PISC score which are equal to 1.

The Inference of the Evolution of Immune Traits as Constrained by Phylogeny: Insight into the Immune System of the Basal Diapsid.

Simple SummaryIn light of emerging pathogenic threats affecting wildlife, it is important to broaden the current understanding of immune system function, development, and evolution. The relation of descent of immune traits is critical to understand the ability of organisms to handle pathogens. Here, we explore the evolution of toll-like receptors (TLRs), a series of receptors crucial to the initial immune response in reptiles. Our analysis revealed that the common ancestor may have had an immune system that lacked two receptors: TLR 15, a receptor uniquely present in Reptilia, and TLR 13, a receptor important in the recognition of pathogens. Additionally, our analysis showed a dynamic evolution for various TLRs, likely attributed to redundancies in function.Among vertebrates, some of the most vulnerable taxa to emergent fungal pathogens are members of Reptilia. In light of the growing threat of emergent fungal pathogens affecting wildlife, it is important to broaden the current understanding of immune system function, development, and evolution. The homologous condition of a trait is necessary in order to study its evolution, as such, homology is necessary in the study of immunological evolution. Here, we explore the evolution of toll-like receptors (TLRs), a series of homologous receptors crucial to the initial immune response. The homologous condition of TLR genes provides a unique system in which to explore the evolution of the TLR; using a Reptilian phylogeny, we elucidate the immune condition of the basal diapsid. Our analysis revealed that the basal diapsid may have had an immune system that lacked two receptors: TLR 15, a receptor uniquely present in Reptilia, and TLR 13, a receptor important in the recognition of nucleic acid motifs. Additionally, our analysis showed multiple losses and convergences for various TLRs, likely attributed to redundancies in receptor function. Further exploration into the immune condition of extinct taxa may shed light on the evolution of the reptilian immune system.

Genome-Wide Scan Reveals Toll-Like Receptor Contraction Events in Oplegnathidae.

The striped knifejaw (Oplegnathus fasciatus) and spotted knifejaw (Oplegnathus punctatus) are prominent members of the Oplegnathidae family and are rocky reef-loving fishes with high ecological and economic value. However, the frequent occurrence of diseases in these fishes has severely restricted the development of their breeding industry. Toll-like receptors (TLRs) play an important role in resistance to pathogens as part of innate immunity. Genome-wide scans and cross-species comparative analysis revealed 10 TLRs in O. fasciatus (OfTLRs) and only 5 in O. punctatus (OpTLRs). In contrast to those of mammals and other fishes, the TLR family of Oplegnathidae underwent significant contraction events, especially in O. punctatus (only TLR1, TLR2, TLR14, TLR5, and TLR21 were retained). A phylogenetic tree divided the 10 OfTLRs into 5 subfamilies: TLR1, TLR3, TLR5, TLR7, and TLR11. The five OpTLR genes were divided into three different subfamilies: TLR1, TLR5, and TLR11. Quantitative real-time PCR revealed that all OpTLRs were expressed in the examined tissues, especially the immune system-related tissues, such as the spleen, gill, head kidney, and middle kidney. The expression of OpTLRs was high at the early stage of development (5 days posthatching [dph]) and decreased gradually until 30 dph. We speculated that maternal immunity or the developmental function of TLRs played an important protective role in the early stage. However, from 30 to 60 dph, TLR expression was low. At this time, juvenile fish are susceptible to viruses and begin to show TLR self-expression with weak immunity. Artificial immunity enhancement is needed to improve the environmental resistance of juvenile fish. In summary, our results not only provide valuable basic data for future studies of the TLR gene family in Oplegnathidae fish but also lay a solid foundation for Oplegnathidae fish research.

Association of Toll-like receptors polymorphisms with the risk of acute lymphoblastic leukemia in the Brazilian Amazon

Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children in childhood. Single-nucleotide polymorphism (SNPs) in key molecules of the immune system, such as Toll-like receptors (TLRs) and CD14 molecules, are associated with the development of several diseases. However, their role in ALL is unknown. A case–control study was performed with 152 ALL patients and 187 healthy individuals to investigate the role of SNPs in TLRs and the CD14 gene in ALL. In this study, TLR6 C > T rs5743810 [OR: 3.20, 95% CI: 1.11–9.17, p = 0.003) and TLR9 C > T rs187084 (OR: 2.29, 95% CI: 1.23–4.26, p = 0.000) seems to be a risk for development of ALL. In addition, the TLR1 T > G rs5743618 and TLR6 C > T rs5743810 polymorphisms with protection against death (OR: 0.17, 95% IC: 0.04–0.79, p = 0.008; OR: 0.48, 95% IC: 0.24–0.94, p = 0.031, respectively). Our results show that SNPs in TLRs genes may be involved in the pathogenesis of ALL and may influence clinical prognosis; however, further studies are necessary to elucidate the role of TLR1, TLR4, TLR5, TLR6, TLR9 and CD14 polymorphisms in this disease.

Genetic Polymorphism in Toll-Like Receptor 3 and Interferon Regulatory Factor 3 in Hepatitis C Virus-Infected Patients: Correlation with Liver Cirrhosis.

Host genetic factors could play a primary role in determining the risk for cirrhosis development in chronic hepatitis C virus (HCV)-infected patients. We designed this work to study the effect of single-nucleotide polymorphism (SNP) in Toll-like receptor 3 (TLR3) and interferon regulatory factor (IRF) on the risk of HCV-related cirrhosis. This study enrolled 139 Egyptian HCV-infected patients. They were divided into patients with cirrhotic (56) and noncirrhotic (83) liver. Genotyping of rs3775291 F459F (+1234C/T) and rs3775290 L412F (+1377C/T) in TLR3 and IRF3 rs2304204 (-925A/G) was performed by restriction fragment length polymorphism-polymerase chain reaction. Although there is no significant difference in genotype and allele distribution of +1377C/T of TLR3 gene between cirrhotic and noncirrhotic subjects, CC (odds ratio [OR] = 1.572, 95% confidence interval [CI]: 0.781-3.164); TT (OR = 1.463, 95% CI: 0.351-6.104) genotypes might be considered as risk factors for liver cirrhosis. On the contrary, the analysis revealed that only one genotype (CC) and one allele (C) were detected in +1234C/T SNP, with the total disappearance of CT/TT genotypes and T allele in all subjects. On the contrary, lower frequency has been found for the AG genotype of the IRF3 (-925A/G) gene in cirrhotic patients compared with noncirrhotic ones, indicating that AG is a protective genotype (OR = 0.509, 95% CI: 0.256-1.012). Our data stressed the association of AG genotype SNP in IRF3 (-925A/G) in protection against the worth outcome of HCV infection.

Polymorphisms in the Genes Coding for TLRs, NLRs and RLRs Are Associated with Clinical Parameters of Patients with Acute Myeloid Leukemia.

Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs) are major elements of the innate immune system that recognize pathogen-associated molecular patterns. Single-nucleotide polymorphisms (SNPs) in the TLR, NLR, and RLR genes may lead to an imbalance in the production of pro- and anti-inflammatory cytokines, changes in susceptibility to infections, the development of diseases, and carcinogenesis. Acute myeloid leukemia (AML) is a bone marrow malignancy characterized by uncontrolled proliferation of transformed myeloid precursors. We retrospectively analyzed 90 AML patients. We investigated the effect of fifteen SNPs located in the genes coding for RLR1 (rs9695310, rs10738889, rs10813831), NOD1 (rs2075820, rs6958571), NOD2 (rs2066845, rs2066847, rs2066844), TLR3 (rs5743305, rs3775296, 3775291), TLR4 (rs4986791, rs4986790), and TLR9 (rs187084, rs5743836). We observed that TLR4 rs4986791, TLR9 rs5743836, and NOD2 rs2066847 were associated with CRP levels, while RLR-1 rs10738889 was associated with LDH level. Furthermore, we found TLR3 rs5743305 AA to be more common in patients with infections. We also found TLR9 rs187084 C to be associated with more favorable risk, and RLR-1 rs9695310 GG with higher age at diagnosis. In conclusion, the current study showed that SNPs in the genes encoding TLRs, NLRs, and RLRs may be potential biomarkers in patients with AML.

Effects of bacteriophage supplement on the growth performance, microbial population, and PGC-1α and TLR4 gene expressions of broiler chickens

Bacteriophages (BP) are viruses that invade bacteria and propagate inside them, leading to the lysis of the bacterial cells. The aim of this study was to investigate the effect of adding BP to the broiler’s diet and its effect on the performance, morphology and bacterial population of the gut, some immune responses and expression of some intestinal genes. Accordingly, dietary treatments were as follows: basal diet (control), and control + 0.3 g/kg colistin or 0.5, 1 and 1.5 g BP/kg of diet. BP increased the body weight gain and reduced the feed conversion ratio (FCR), as compared to the colistin treatment, in the finisher and overall period (P < 0.05). European efficiency factor was significantly higher in 1.5 g BP-fed birds, as compared to the control and colistin treatments. meanwhile, bacteriophage and colistin-fed birds had higher Lactobacillus and lowered coliform bacteria counts, as compared to the control treatment (P < 0.05). Cecal concentrations of propionate in the 1.5 g BP-fed birds were higher than those in the control treatment (P < 0.05). BP-fed birds had a significantly increased villus height to crypt depth ratio, as compared to the control treatment. BP increased the serum concentrations of the total antibody, immunoglobulin (Ig) M, and IgG, as compared to the control treatment (P < 0.05). In the ileum, the expression of the Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) gene was decreased by dietary BP supplementation (P < 0.05). Furthermore, Toll-like receptor 4 (TLR4) gene expression was down-regulated in the BP-fed birds, whereas Interleukin 10 (IL-10) gene expression was up-regulated (P < 0.05). Overall, the use of BP may be a promising alternative to growth-promoting antibiotics in broilers by altering the gastrointestinal tract microbiota, enhancing immunological responses and improving the gut's morphology.