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1.
Nat Commun ; 10(1): 2830, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31249303

RESUMO

Cytomegalovirus is a DNA-encoded ß-herpesvirus that induces STING-dependent type 1 interferon responses in macrophages and uses myeloid cells as a vehicle for dissemination. Here we report that STING knockout mice are as resistant to murine cytomegalovirus (MCMV) infection as wild-type controls, whereas mice with a combined Toll-like receptor/RIG-I-like receptor/STING signaling deficiency do not mount type 1 interferon responses and succumb to the infection. Although STING alone is dispensable for survival, early IFN-ß induction in Kupffer cells is STING-dependent and controls early hepatic virus propagation. Infection experiments with an inducible reporter MCMV show that STING constrains MCMV replication in myeloid cells and limits viral dissemination via these cells. By contrast, restriction of viral dissemination from hepatocytes to other organs is independent of STING. Thus, during MCMV infection STING is involved in early IFN-ß induction in Kupffer cells and the restriction of viral dissemination via myeloid cells, whereas it is dispensable for survival.


Assuntos
Infecções por Herpesviridae/veterinária , Interferon beta/metabolismo , Fígado/metabolismo , Proteínas de Membrana/metabolismo , Muromegalovirus/fisiologia , Células Mieloides/metabolismo , Doenças dos Roedores/metabolismo , Animais , Feminino , Hepatócitos/metabolismo , Hepatócitos/virologia , Infecções por Herpesviridae/virologia , Interações Hospedeiro-Patógeno , Interferon beta/genética , Macrófagos do Fígado/metabolismo , Macrófagos do Fígado/virologia , Fígado/virologia , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Muromegalovirus/genética , Células Mieloides/virologia , Doenças dos Roedores/genética , Doenças dos Roedores/virologia , Transdução de Sinais , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo
2.
Fish Shellfish Immunol ; 90: 134-140, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31055019

RESUMO

Toll-like receptors (TLRs) are a large family of pattern recognition receptors (PRRs) that play a critical role in innate immunity. TLRs are activated when they recognize microbial associated molecular patterns (MAMPs) of bacteria, viruses, or fungus. In the present study, two TLRs were isolated from the mantle of the hard-shelled mussel (Mytilus coruscus) and designated McTLR2 and McTLR3 based on their sequence similarity and phylogenetic clustering with Crassostrea gigas, CgiTLR2 and CgiTLR3, respectively. Quantitative RT-PCR analysis demonstrated that McTLR2 and McTLR3 were constitutively expressed in many tissues but at low abundance.


Assuntos
Hemócitos/imunologia , Imunidade Inata/genética , Mytilus/genética , Mytilus/imunologia , Receptores Toll-Like/genética , Receptores Toll-Like/imunologia , Sequência de Aminoácidos , Animais , Perfilação da Expressão Gênica , Hemócitos/metabolismo , Filogenia , Alinhamento de Sequência , Receptores Toll-Like/química
3.
Environ Sci Pollut Res Int ; 26(17): 17797-17808, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31037535

RESUMO

Efficacy of Metarhizium anisopliae strain (IMI330189) and Mad1 protein alone or in combination by feeding method to overcome immune-related enzymes and Toll-like pathway genes was investigated in migratory locust. M. anisopliae (IMI330189) is a potent and entomopathogenic fungal strain could be effectively used against insect pests. Similarly, Mad1 protein adheres to insect cuticle, causing virulence to insects. We confirmed maximum 55% of mortality when M. anisopliae (IMI330189) and Mad1 was applied in combination. Similarly, increased PO activity was observed in locust with combined dose of Mad1 + IMI330189 whereas PO, POD, and SOD activities reduced using Mad1 independently. Four Toll-like signaling pathway genes (MyD88, Cactus, Pelle, and CaN) were investigated from midgut and body of the migratory locust after 72 h of treatments. Subsequently, the expression of MyD88 in the midgut and body significantly decreased with the application of Mad1 and Mad1 + IMI330189. Performance of these treatments was absolutely non-consistent in both parts of insects. Meanwhile, IMI330189 significantly raised the expression of Cactus in both midgut and body. However, the combined treatment (Mad1 + IMI330189) significantly reduced the Cactus expression in both body parts. Pelle expression was significantly increased in the midgut with the application of independent treatment of Mad1 and IMI330189 whereas the combined treatment (Mad1 + IMI330189) suppressed the Pelle expression in midgut. Its expression level was absolutely higher in body with the application of IMI330189 and Mad1 + IMI330189 only. On the other hand, Mad1 significantly increased the expression of CaN in midgut. However, all three treatments significantly affected and suppressed the expression of CaN gene in body of locust. This shows that the applications of M. anisopliae and Mad1 protein significantly affected Toll signaling pathway genes, which ultimately increased level of susceptibility of locust. However, their effect was significantly different in both parts of locust which recommends that the Toll-related genes are conserved in midgut instead of locust body.


Assuntos
Proteínas Fúngicas/metabolismo , Gafanhotos/microbiologia , Metarhizium , Migração Animal , Animais , Genes de Insetos , Gafanhotos/enzimologia , Controle de Insetos/métodos , Insetos , Receptores Toll-Like/genética , Virulência
4.
Scand J Immunol ; 90(1): e12771, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31054156

RESUMO

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). I602S (TLR1), R677W (TLR2), P554S (TLR3), D299G (TLR4), F616L (TLR5), S249P (TLR6), Q11L (TLR7), M1V (TLR8), G1174A (TLR9) and G1031T (TLR10) 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.


Assuntos
Doenças Transmissíveis/genética , Receptores Toll-Like/genética , Animais , Predisposição Genética para Doença , Humanos , Imunidade/genética , Vigilância Imunológica , Padrões Moleculares Associados a Patógenos/imunologia , Polimorfismo Genético , Relação Estrutura-Atividade
5.
J Microbiol Biotechnol ; 29(6): 863-876, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31091863

RESUMO

Farm animals such as piglets are often affected by environmental stress, which can disturb the gut ecosystem. Antibiotics were commonly used to prevent diarrhea in weaned piglets, but this was banned by the European Union due to the development of antibiotic resistance. However, the use of probiotics instead of antibiotics may reduce the risk posed by pathogenic microorganisms and reduce the incidence of gastrointestinal diseases. Therefore, this study was conducted to investigate the effects of Lactobacillus casei Zhang on the mechanical barrier and immune function of early-weaned piglets infected using Escherichia coli K88 based on histomorphology and immunology. Fourteen-day-old weaned piglets were divided into a control group and experimental groups that were fed L. casei Zhang and infected with E. coli K88 with or without prefeeding and/or postfeeding of L. casei Zhang. The L. casei Zhang dose used was 107 CFU/g diet. Jejunum segments were obtained before histological, immunohistochemical, and western blot analyses were performed. In addition, the relative mRNA expression of toll receptors and cytokines was measured. Piglets fed L. casei Zhang showed significantly increased jejunum villus height, villus height-crypt depth ratio, muscle thickness, and expression of proliferating cell nuclear antigen and tight junction proteins ZO-1 and occludin. The use of L. casei Zhang effectively reduced intestinal inflammation after infection. We found that L. casei Zhang feeding prevented the jejunum damage induced by E. coli K88, suggesting that it may be a potential alternative to antibiotics for preventing diarrhea in early-weaned piglets.


Assuntos
Infecções por Escherichia coli/veterinária , Expressão Gênica/efeitos dos fármacos , Mucosa Intestinal/fisiologia , Jejuno/efeitos dos fármacos , Lactobacillus casei/fisiologia , Probióticos/administração & dosagem , Doenças dos Suínos/prevenção & controle , Animais , Citocinas/genética , Suplementos Nutricionais , Escherichia coli Enterotoxigênica/fisiologia , Infecções por Escherichia coli/patologia , Infecções por Escherichia coli/prevenção & controle , Fatores Imunológicos/genética , Fatores Imunológicos/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Jejuno/patologia , Ocludina/genética , Ocludina/metabolismo , Probióticos/farmacologia , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Suínos , Doenças dos Suínos/patologia , Receptores Toll-Like/genética , Desmame , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismo
6.
Microb Pathog ; 133: 103550, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31112773

RESUMO

Diversity of Campylobacter and Salmonella strains in interaction with epithelial cells may explain distinct modes of the pathogenesis, varying from mild watery to severe inflammatory diarrhea. We analyzed impact of this diversity, in relation to carriage and expression of cytholethal distending toxin B (cdtB), on alteration of IL-8, TNF-α, TLR2, TLR4, TLR5, CASP3 mRNA and cytokine levels in HT-29 cell line. A diversity was observed for induction of genes among different strains. Great diversity in IL-8 induction was detected between cdtB+ and cdtB- strains. Early analysis showed down-regulation of TNF-α, mostly among cdtB+ strains. Any increase or decrease in expression of TLR2 in the cdtB-C. jejuni strains was orderly correlated with increase or decrease of TLR4 and TNF-α. Up-regulation of CASP3 was followed by upregulation of TLR2, -4 and/or TNF-α, regardless to the cdtB status. In conclusion, induction of inflammatory response could mediate by distinct C. jejuni and S. enterica strains by several ways.


Assuntos
Campylobacter jejuni/genética , Citocinas/genética , Fezes/microbiologia , Microbiologia de Alimentos , Salmonella enterica/genética , Receptores Toll-Like/genética , Transcriptoma/genética , Apoptose/genética , Proteínas de Bactérias/genética , Toxinas Bacterianas/genética , Infecções por Campylobacter , Caspase 3/metabolismo , Diarreia/microbiologia , Células Epiteliais , Células HT29 , Humanos , Inflamação , Interleucina-8/metabolismo , RNA Mensageiro , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Receptor 5 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima
7.
Fish Shellfish Immunol ; 90: 297-307, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059811

RESUMO

Toll-like receptors (TLRs) play an important role in defense response to pathogens in mollusk. In this study the first TLR from Sepiella japonica (named as SjTLR) was functionally characterized, and its full-length cDNA consisted of 3914bp (GenBank accession no. AQY56780.1) including an open reading frame of 3582bp, encoding a putative protein of 1193 amino acids. Its theoretical molecular weight was 137.87 KDa and the predicted isoelectric point was 3.69. The derived amino acids sequence comprised of an extracellular domain including 26 amino acids signal peptide and eleven leucine-rich repeats (LRR), capped with LRRCT and LRRNT followed by transmembrane domain and cytoplasmic Toll/IL-1R domain (TIR). In addition, 12 potential N-linked glycosylation sites were present in the ectodomain to influence protein trafficking, surface presentation and ligand recognition. Multiple sequence alignment and phylogenetic analysis revealed that SjTLR shared the highest similarity to that of Euprymna scolopes and they fell into the same clade. Real-time PCR showed SjTLR expressed constitutively in all tested tissues, including gill, liver, brain, muscle, intestine, heart, lobus opticus and stomach, but showed different expression levels with genders. The highest expression was in the liver, and the lowest was in stomach for both genders. The functional domain region sequences encoding LRRs domain protein and TIR domain containing protein (TcpB) were expressed in BL21(DE3) respectively and purified with Ni-NAT Superflow resin conforming to the expected molecular weight. The cellular localization of SjTLR in HEK293 cells was conducted and plasma membrane localization was detected. SjLRRs internalization upon the activation of LPS was also observed, and dramatic redistribution of SjLRRs in the cytoplasm with distinct perinuclear accumulation was found. After SjTLR transfection Toll/NF-κB signaling pathway was active in HEK293 treated with LPS and TNFɑ. The nuclear related genes may also be activated by NF-κB in the nucleus, and the corresponding mRNA was transferred through the intracellular signal transduction pathway, so that IL-6 cytokines could be synthesized and released. After infection by Vibrio parahemolyticus and Aeromonas hydrophila the expression of SjTLR were upregulated with time-dependent manner. These findings might be valuable for understanding the innate immune signaling pathways of S.japonica and enabling future studies on host-pathogen interactions.


Assuntos
Decapodiformes/genética , Decapodiformes/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Receptores Toll-Like/genética , Receptores Toll-Like/imunologia , Aeromonas hydrophila/fisiologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Perfilação da Expressão Gênica , Células HEK293 , Humanos , Filogenia , Alinhamento de Sequência , Transdução de Sinais , Receptores Toll-Like/química , Vibrio parahaemolyticus/fisiologia
8.
Curr Top Microbiol Immunol ; 421: 139-158, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31123888

RESUMO

Infectious diseases have been paramount among the threats to human health and survival throughout evolutionary history. Bacterial cell-surface molecules are key factors in the microorganism-host crosstalk, as they can interact with host pattern-recognition receptors (PRRs) of the gastrointestinal mucosa. The best-studied PRRs are toll-like receptors (TLRs). Because TLRs play an important key role in host defense, they have received increasing interest in the evolutionary and population genetics literature, and their variation represents a potential target of adaptive evolution. Helicobacter pylori is one of the commensal bacteria in our body and can have pathogenic properties in a subset of infected people. The history of H. pylori research indicated that humans and bacteria co-evolved during evolution. A genome-wide association study (GWAS) has opened the way for investigating the genomic evolution of bacterial pathogens during the colonization and infection of humans. Recent GWAS research emphasized the importance of TLRs, especially TLR10 during pathogenesis in H. pylori infection. We demonstrated that TLR10, whose ligand was unknown for a long time, can recognize H. pylori LPS. Our results of H. pylori research suggest that TLR10 might play an important role to also recognize other commensal bacteria. In this review, we discuss the importance of TLRs in pro-inflammatory and anti-inflammatory responses by H. pylori infection. Especially, we highlight the TLR10 interaction with H. pylori infection, providing new insights about TLR10 signaling.


Assuntos
Anti-Inflamatórios/imunologia , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Helicobacter pylori/patogenicidade , Mediadores da Inflamação/imunologia , Receptores Toll-Like/imunologia , Evolução Molecular , Estudo de Associação Genômica Ampla , Infecções por Helicobacter/genética , Humanos , Receptores Toll-Like/genética
9.
Chem Biol Interact ; 305: 119-126, 2019 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-30935901

RESUMO

Epidemiological and toxicological studies indicate that polyhexamethylene guanidine phosphate (PHMG-p) is a guanidine-based cationic disinfectant strongly associated with interstitial lung diseases. As individuals exposed to aerosolized PHMG-p complain of respiratory problems (asthma and rhinitis), whether PHMG-p can cause respiratory diseases other than interstitial fibrosis should be investigated. MUC5AC, the predominant mucin gene expressed in airways, is associated with obstructive respiratory disease pathogenesis. Therefore, in this study, we elucidated the relationship between PHMG-p and MUC5AC overexpression. First, in immunofluorescence studies, the bronchial epithelia of mice intratracheally administrated PHMG-p appeared to be sloughing and tethered by MUC5AC. Second, Calu-3 cells exposed to PHMG-p showed concentration-dependent increases in MUC5AC mRNA and protein expression. c-Jun N-terminal kinase (JNK), p38, and c-jun were phosphorylated in cells exposed to PHMG-p. SP600125 and SB203580, JNK and p38 inhibitors, respectively, reduced the upregulation of MUC5AC by PHMG-p in Calu-3 cells. When toll-like receptor (TLR)2, 4, and 6 were silenced, PHMG-p-induced JNK and p38 phosphorylation decreased. Furthermore, TLR2-, 4-, and 6-silenced cells showed reduced levels of MUC5AC mRNA and protein induced by PHMG-p, with TLR6 knockdown showing the greatest effect. In conclusion, PHMG-p induced MUC5AC overexpression via activation of the TLR-p38 MAPK and JNK axis.


Assuntos
Guanidinas/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Mucina-5AC/metabolismo , Receptores Toll-Like/metabolismo , Regulação para Cima/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Brônquios/citologia , Brônquios/metabolismo , Brônquios/patologia , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mucina-5AC/genética , Muco/metabolismo , Fosforilação/efeitos dos fármacos , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptores Toll-Like/antagonistas & inibidores , Receptores Toll-Like/genética , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
10.
Gene ; 702: 166-170, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-30935923

RESUMO

TLRs are thought to play a role in the pathophysiology of such dermatological diseases as leprosy, acne and psoriasis. The study included 20 patients with plaque psoriasis, as well as 20 healthy age- and gender-matched control subjects. Real-time polymerase chain reaction evaluation was made of the messenger RNA expression of TLRs 1-10 in lesional tissue and peripheral blood mononuclear cell samples in psoriasis patients. TLR 3, 5, 6, 7, 9 and 10 lesional tissue mRNA expressions were increased significantly when compared to the expression levels in the PBMCs of the same patients (p = 0.0082, p = 0.0176, p = 0.0239, p = 0.0261, p = 0.0223, p = 0.0206). A comparison of the TLR expression in the PBMCs of healthy subjects and the PBMCs of patients with psoriasis showed a significant increase in the TLR 1, 8 and 10 mRNA expressions in the patient group (p < 0.0001, p < 0.0001, p = 0.0035). The TLR 5 mRNA expression was significantly higher in the control group than in the patient group (p = 0.0037). To the best of our knowledge, this is the first study in literature to evaluate mRNA TLR expression levels in the lesional tissue and PBMCs of patients with psoriasis.


Assuntos
Psoríase/metabolismo , Receptores Toll-Like/metabolismo , Adulto , Feminino , Expressão Gênica , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Psoríase/sangue , Psoríase/genética , Receptor 1 Toll-Like/sangue , Receptor 1 Toll-Like/genética , Receptor 10 Toll-Like/sangue , Receptor 10 Toll-Like/genética , Receptor 8 Toll-Like/sangue , Receptor 8 Toll-Like/genética , Receptores Toll-Like/sangue , Receptores Toll-Like/genética
11.
PLoS Negl Trop Dis ; 13(4): e0007287, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30986216

RESUMO

Mosquitoes act as vectors of numerous pathogens that cause human diseases. Dengue virus (DENV) transmitted by mosquito, Aedes aegypti, is responsible for dengue fever epidemics worldwide with a serious impact on human health. Currently, disease control mainly relies on vector targeted intervention strategies. Therefore, it is imperative to understand the molecular mechanisms underlying the innate immune response of mosquitoes against pathogens. In the present study, the expression profiles of immunity-related genes in the midgut responding to DENV infection by feeding were analyzed by transcriptome and quantitative real-time PCR. The level of Antimicrobial peptides (AMPs) increased seven days post-infection (d.p.i.), which could be induced by the Toll immune pathway. The expression of reactive oxygen species (ROS) genes, including antioxidant genes, such as HPX7, HPX8A, HPX8B, HPX8C were induced at one d.p.i. and peaked again at ten d.p.i. in the midgut. Interestingly, down-regulation of the antioxidant gene HPX8C by RNA interference led to reduction in the virus titer in the mosquito, probably due to the elevated levels of ROS. Application of a ROS inhibitor and scavenger molecules further established the role of oxygen free radicals in the modulation of the immune response to DENV infection. Overall, our comparative transcriptome analyses provide valuable information about the regulation of immunity related genes in the transmission vector in response to DENV infection. It further allows us to identify novel molecular mechanisms underlying the host-virus interaction, which might aid in the development of novel strategies to control mosquito-borne diseases.


Assuntos
Aedes/genética , Aedes/imunologia , Imunidade Inata , Peroxidase/genética , Aedes/virologia , Animais , Peptídeos Catiônicos Antimicrobianos/genética , Dengue/imunologia , Vírus da Dengue , Sistema Digestório/imunologia , Sistema Digestório/virologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Heme/genética , Heme/imunologia , Interações entre Hospedeiro e Microrganismos , Camundongos , Peroxidase/imunologia , Interferência de RNA , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais , Organismos Livres de Patógenos Específicos , Receptores Toll-Like/genética
12.
J Agric Food Chem ; 67(17): 5033-5042, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30964671

RESUMO

Many studies have shown that fluorosis due to long-term fluoride intake has damaging effects on the heart. However, the mechanisms underlying cardiac fluorosis have not been illuminated in detail. We performed high-throughput transcriptome sequencing (RNA-Seq) on rat cardiac tissue to explore the molecular effects of NaF exposure. In total, 372 and 254 differentially expressed genes (DEGs) were identified between a group given 30 mg/L NaF and control and between a group given 90 mg/L NaF and control, respectively. The transcript levels of most of these genes were significantly down-regulated and many were distributed in the Toll-like receptor signaling pathway. Transcriptome analysis revealed that herpes simplex infection, ECM-receptor interaction, influenza A, cytokine-cytokine receptor interaction, apoptosis, and Toll-like receptor signaling pathway were significantly affected. IL-6 and IL-10 may play a crucial role in the cardiac damage caused by NaF as external stimuli according to protein-protein interaction (PPI) network analysis. The results of qRT-PCR and Western blotting showed a marked decreased mRNA and protein levels of IL-1, IL-6, and IL-10 in the low concentration fluoride (LF) and high concentration fluoride (HF) groups, which was in agreement with RNA-Seq results. This is the first study to investigate NaF-induced cardiotoxicity at a transcriptome level.


Assuntos
Cardiotoxicidade/etiologia , Cardiotoxicidade/metabolismo , Fluoretos/toxicidade , Receptores Toll-Like/metabolismo , Animais , Cardiotoxicidade/genética , Perfilação da Expressão Gênica , Humanos , Interleucina-1/genética , Interleucina-1/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Ligação Proteica/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Receptores Toll-Like/genética
13.
Fish Shellfish Immunol ; 89: 132-140, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30930276

RESUMO

Toll-like receptors (TLRs) are a category of most well recognized pattern recognition molecules that act on a vital role in both innate and adaptive immunity. In the present study, a novel toll-like receptor (McTLRw) was identified and characterized in thick shell mussel Mytilus coruscus. McTLRw possesses one intracellular Toll/interleukin-1 (IL-1) receptor (TIR) domain, one transmembrane region (TM), one leucine rich repeat N-terminal domain (LRR_NT) and a few of leucine-rich repeats (LRRs), which all are common in typical TLRs. McTLRw transcripts were constitutively expressed in all examined tissues with higher expression levels in immune related tissues, and were significantly induced in haemocytes with the challenges of live Vibrio alginolyticus, lipopolysaccharide (LPS), peptidoglycans (PGN) and ß-glucan (GLU), but not induced by polyinosinic-polycytidylic acid (poly I:C). rMcTLRw exhibited affinity to LPS, PGN and GLU while no affinity to poly I:C. Further, the downstream of TLR signaling pathway myeloid differentiation factor 88a (MyD88a), interleukin-1 receptor-associated kinase-4 (IRAK4) and tumor necrosis factor receptor-associated factor 6 (TRAF6) were significantly repressed in McTLRw silenced mussels while challenged with LPS. These results collectively indicated that McTLRw is one member of TLR family and involved in immune response to against invaders by taking participate in TLR mediated signaling pathway.


Assuntos
Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Mytilus/genética , Mytilus/imunologia , Receptores Toll-Like/genética , Receptores Toll-Like/imunologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Perfilação da Expressão Gênica , Lipopolissacarídeos/farmacologia , Peptidoglicano/farmacologia , Filogenia , Receptores Toll-Like/química , Vibrio alginolyticus/fisiologia , beta-Glucanas/farmacologia
14.
Artigo em Inglês | MEDLINE | ID: mdl-30825647

RESUMO

Toll-like receptors (TLRs) play crucial roles in the host immune system, including recognizing invading pathogenic microbes and triggering immune reactions. Toll-like receptor 14 (TLR14) has been identified in several fish species, but its function requires further study. In this study, TLR14 (designed as ToTLR14) from golden pompano (Trachinotus ovatus), was characterized and investigated its expression responses to three types of pathogen-associated molecular patterns. The full-length ToTLR14 cDNA was 3191 bp, and the deduced protein consisted of 876 amino acids. The ToTLR14 protein included 5 leucine rich repeat (LRR) domains, a C-terminal LRR domain in the extracellular region, a transmembrane domain and a Toll/interleukin (IL)-1 receptor (TIR) domain in the cytoplasmic region, which fits with the typical TLR domain architecture. The genomic organization of ToTLR14 was also identified and consisted of four introns and five exons. The predicted promoter region of ToTLR14 contained several putative transcription factor binding sites. Phylogenetic analysis showed that ToTLR14 was clustered into the TLR1 subfamily clade. Quantitative real-time (qRT-PCR) analysis indicated that ToTLR14 were ubiquitously expressed in all examined tissues, with higher mRNA levels observed in the skin, kidney and intestine, while the lowest level was detected in the stomach. After injection with polyinosinic:polycytidylic acid [poly(I:C)], flagellin or lipopolysaccharides (LPS), the expression level of ToTLR14 mRNA were significantly upregulated in various tissues of golden pompano. These results indicate that ToTLR14 may play an important role in systemic as well as mucosal defence after viral and bacterial stimulation.


Assuntos
Proteínas de Peixes , Peixes , Regulação da Expressão Gênica/imunologia , Filogenia , Receptores Toll-Like , Animais , DNA Complementar/genética , Éxons , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Peixes/genética , Peixes/imunologia , Íntrons , Especificidade de Órgãos/fisiologia , Domínios Proteicos , Receptores Toll-Like/genética , Receptores Toll-Like/imunologia
15.
J Immunol Res ; 2019: 8197048, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30863783

RESUMO

Innate immunity represents the first barrier against bacterial invasion. Toll-like receptors (TLRs) belong to the large family of pattern recognition receptors (PRRs), and their activation leads to the induction of inflammatory cytokines, chemokines, antigen-presenting molecules, and costimulatory molecules. Recent studies have focused on identifying the association between TLRs and Helicobacter pylori- (H. pylori-) related diseases. Therefore, this minireview focuses on assessing the role of these TLRs in the development of H. pylori-related gastropathies. Both TLR2 and TLR were found to be involved in H. pylori LPS recognition, with contradictory results most likely due to both the inability to obtain pure LPS in experimental studies and the heterogeneity of the bacterial LPS. In addition, TLR2 was found to be the most extensively expressed gene among all the TLRs in gastric tumors. High levels of TLR4 were also associated with a higher risk of gastric cancer. TLR5 was initially associated with the recognition of H. pylori flagellin, but it seems that this bacterium has developed mechanisms to escape this recognition representing an important factor involved in the persistence of this infection and subsequent carcinogenesis. TLR9, the only TLR with both anti- and proinflammatory roles, was involved in the recognition of H. pylori DNA. The dichotomous role of TLR9, promoting or suppressing the infection, depends on the gastric environment. Recently, TLR7 and TLR8 were shown to recognize purified H. pylori RNA, thereby inducing proinflammatory cytokines. TLR1 and TLR10 gene polymorphisms were associated with a higher risk for gastric cancer in H. pylori-infected individuals. Different gene polymorphisms of these TLRs were found to be associated with gastric cancer depending mostly on ethnicity. Further studies are required in order to develop preventive and therapeutic strategies against H. pylori infections based on the functions of TLRs.


Assuntos
Gastroenteropatias/imunologia , Gastroenteropatias/microbiologia , Infecções por Helicobacter/imunologia , Receptores Toll-Like/imunologia , Animais , Grupos Étnicos , Infecções por Helicobacter/complicações , Helicobacter pylori/imunologia , Humanos , Imunidade Inata , Camundongos , Polimorfismo Genético , Receptores de Reconhecimento de Padrão/imunologia , Fatores de Risco , Transdução de Sinais , Neoplasias Gástricas/microbiologia , Receptores Toll-Like/genética
16.
PLoS Genet ; 15(3): e1007931, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30822306

RESUMO

Dipteran insects transmit serious diseases to humans, often in the form of trypanosomatid parasites. To accelerate research in more difficult contexts of dipteran-parasite relationships, we studied the interaction of the model dipteran Drosophila melanogaster and its natural trypanosomatid Herpetomonas muscarum. Parasite infection reduced fecundity but not lifespan in NF-κB/Relish-deficient flies. Gene expression analysis implicated the two NF-κB pathways Toll and Imd as well as STAT signalling. Tissue specific knock-down of key components of these pathways in enterocytes (ECs) and intestinal stem cells (ISCs) influenced initial numbers, infection dynamics and time of clearance. Herpetomonas triggered STAT activation and proliferation of ISCs. Loss of Relish suppressed ISCs, resulting in increased parasite numbers and delayed clearance. Conversely, overexpression of Relish increased ISCs and reduced uptake. Finally, loss of Toll signalling decreased EC numbers and enabled parasite persistence. This network of signalling may represent a general mechanism with which dipteran respond to trypanosomatids.


Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Interações Hospedeiro-Parasita/genética , Fatores de Transcrição/genética , Trypanosomatina/genética , Animais , Proliferação de Células/genética , Drosophila melanogaster/parasitologia , Enterócitos/metabolismo , Enterócitos/parasitologia , Fertilidade/genética , Regulação da Expressão Gênica/genética , Humanos , Intestinos/parasitologia , Fatores de Transcrição STAT/genética , Transdução de Sinais/genética , Células-Tronco/metabolismo , Receptores Toll-Like/genética , Fator de Transcrição RelA/genética , Trypanosomatina/patogenicidade
17.
Poult Sci ; 98(7): 3022-3028, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30915472

RESUMO

Sustained production of good quality eggs for longer production cycles is a challenge for poultry farms. The impact of aging on the mucosal immune defense in the isthmus and uterus of hens, where the eggshell membrane and eggshell are formed, remains obscure. Thus, the aim of this study was to determine whether aging affects the mucosal tight junction (TJ) proteins, the synthesis of antimicrobial peptides including avian ß-defensins (AvBDs) and cathelicidins (CATHs), and Toll-like receptors (TLRs) in the isthmus and uterus of laying hens. Young and aged White Leghorn laying hens (35 and 130 wk old, respectively) were used. Total RNA and protein contents were isolated from the isthmic and uterine mucosae of these hens to examine the expression of TJ proteins, AvBD, and CATH genes and AvBD proteins by the real-time polymerase chain reaction and western blotting. The results showed that the mRNA expression of TJ proteins, namely zonula occludin 2 in the isthmus and occludin in the uterus, was higher in aged hens than in young hens. Expression of 2 AvBD genes in the isthmus and 4 AvBD genes in the uterus was higher in aged hens than in young hens. However, the expression of AvBD proteins 1 and 11 was not altered by aging. Expressions of CATH genes were not affected by aging in the isthmus or uterus. Expression of TLR genes was higher in aged hens than in young hens in the isthmus, while their expression in the uterus was not affected by aging. It can be concluded that aged hens have a higher potential ability to express TJ proteins and AvBDs for mucosal defense in the isthmic and uterine mucosae than in young hens.


Assuntos
Envelhecimento/metabolismo , Galinhas/fisiologia , Imunidade Inata/imunologia , Útero/metabolismo , Animais , Catelicidinas/genética , Catelicidinas/metabolismo , Feminino , Expressão Gênica , Imunidade Inata/genética , Membrana Mucosa , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo , beta-Defensinas/genética , beta-Defensinas/metabolismo
18.
Fish Shellfish Immunol ; 87: 478-489, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30716519

RESUMO

Toll-like receptors (TLRs) recognizing specific pathogen-associated molecular patterns play crucial roles in immune defence against pathogen invasion. Although recent advances in many species have reported the characterization and functional roles of TLRs in innate immunity, systematic knowledge of TLRs is still lacking in the Chinese soft-shelled turtle Pelodiscus sinensis. In this study, a genome-wide search was performed and identified 15 candidate PsTLR family genes in P. sinensis. Protein structure analysis revealed the conserved domain arrangements for these PsTLR proteins. Phylogenetic analysis indicated the evolutionary conservation of TLRs among various species. Additionally, a putative interaction network among PsTLR proteins was proposed and several functional partner proteins involved in TLR signalling pathway were predicted in P. sinensis. Expression profiling showed that these PsTLRs exhibited constitutive expression patterns in different tissues of P. sinensis. Moreover, several genes were highly expressed in the major immune organ spleen. Remarkably, the mRNA levels of PsTLR2-1, PsTLR4 and several TLR signalling molecules were significantly up-regulated in the spleen after Aeromonas hydrophila infection, indicating that PsTLRs and these genes responded to bacterial stress. These results provide rich information for the functional exploration of PsTLRs and will facilitate uncovering the molecular mechanisms underlying immune regulation in P. sinensis.


Assuntos
Regulação da Expressão Gênica/imunologia , Estudo de Associação Genômica Ampla/veterinária , Imunidade Inata/genética , Receptores Toll-Like/genética , Receptores Toll-Like/imunologia , Tartarugas/genética , Tartarugas/imunologia , Aeromonas hydrophila/fisiologia , Animais , Perfilação da Expressão Gênica/veterinária , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Proteínas de Répteis/genética , Proteínas de Répteis/imunologia
19.
Fish Shellfish Immunol ; 87: 600-608, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30738147

RESUMO

A 70-day feeding trial was conducted to investigate the effects of dietary fish oil (FO) replaced by palm oil (PO) on growth, biochemical and antioxidant response as well as inflammatory response in the liver of large yellow croaker (initial weight 15.87 ±â€¯0.14 g). Four iso-proteic and iso-lipidic experimental diets were formulated with 0% (the control group), 33.3%, 66.7% and 100% FO replaced by PO. Fish fed the diet with 100% PO showed significantly lower growth performance than the control group. As expected, the contents of C16:0, C18:1n-9 and C18:2n-6 were increased with increasing dietary PO levels. There were remarkable increases in total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels in fish fed the diet with 100% PO compared to the control group. Moreover, dietary PO significantly increased activities of plasma alanine transaminase (ALT) and aspartate aminotransferase (AST) in fish fed the diet with 100% PO compared to the control group. The total antioxidant capacity (T-AOC) and the activity of catalase (CAT) in plasma were significantly decreased in fish fed the diet with 100% PO compared to the control group, and meanwhile no significant differences were found in T-AOC and CAT activity in fish fed diets with no more than 66.7% PO. Fish fed the diet with 100% PO exerted significantly higher toll like receptors (TLRs) and myeloid differentiation factor (MyD88) mRNA expression levels than the control group. The IFNγ, IL-1ß and TNFα mRNA expressions were increased with increasing dietary PO levels. The increase of pro-inflammatory gene expression may be due to the activation of NF-κB signaling as the ratio of nucleus p65 to total p65 protein was elevated with the increase of dietary PO levels. These results showed that relatively higher PO levels in diets suppressed the growth and antioxidant capacity as well as induced the inflammatory response by activating TLR-NF-κB signaling pathway in juvenile large yellow croaker.


Assuntos
Gorduras Insaturadas na Dieta/metabolismo , Doenças dos Peixes/imunologia , Inflamação/veterinária , Óleo de Palmeira/metabolismo , Perciformes/fisiologia , Transdução de Sinais/efeitos dos fármacos , Ração Animal/análise , Animais , Antioxidantes/metabolismo , Dieta/veterinária , Gorduras Insaturadas na Dieta/administração & dosagem , Doenças dos Peixes/induzido quimicamente , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Inflamação/induzido quimicamente , Inflamação/imunologia , NF-kappa B/genética , NF-kappa B/metabolismo , Óleo de Palmeira/administração & dosagem , Perciformes/genética , Perciformes/crescimento & desenvolvimento , Perciformes/imunologia , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo
20.
BMC Biol ; 17(1): 15, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30786893

RESUMO

A paper published in BMC Biology characterises biophysically oligomeric and filamentous structures formed spontaneously by the Toll-like receptor signalling adaptor MyD88. Naturally occurring mutants of MyD88 that cause immunodeficiency are unable to form these structures. By contrast a somatic mutant that promotes the survival of tumour cells forms oligomers much more readily than the wild-type protein. These findings suggest that assembly of oligomeric MyD88 is critical for the regulation of inflammatory signalling.


Assuntos
Fator 88 de Diferenciação Mieloide/química , Receptores Toll-Like/genética , Sistema Imunitário , Mutação , Transdução de Sinais/imunologia
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