Role of toll-like receptors gene polymorphism in renal transplantation

Abstract

Toll-like receptors (TLRs), evolutionarily conserved innate, are expressed in a wide variety of tissues and cell types, and they play key role in the innate immune system. Gene mutation is an important factor associated with some diseases risk and gene polymorphism of TLRs can influence their function to take part in the physiological process in the body. Chronic kidney disease causes high morbidity and mortality, and renal transplantation provides the optimal treatment for people with end-stage renal disease. Innate immune takes a most important role in renal transplantation. There are some studies reporting that TLRs gene polymorphism takes an important role in the renal transplantation. However, no review summed up the role of TLRs gene polymorphism in renal transplantation. The literatures were searched extensively and this review was performed to review the role of TLRs gene polymorphism in renal transplantation.     

Role of toll-like receptors in lung cancer

Abstract

Lung cancer is a leading cause of death world-wide and the long-term survival rate for patients with lung cancer is one of the lowest for any cancer. Toll-like receptors (TLRs), evolutionarily conserved innate, are expressed in a wide variety of tissues and cell types, and they play key role in the innate immune system. TLRs have been found to be expressed by some kinds of tumor cells. However, what is the biological function of TLRs on tumor cells and whether human lung cancer cells can express TLRs remain to be fully understood. This review was performed to sum up the role of TLRs in lung cancer.     

Role of toll-like receptors in tissue repair and tumorigenesis

Toll-like receptors (TLRs) play a critical role in host defense from microbial infection. TLRs recognize conserved molecular structures produced by microorganisms and induce activation of innate and adaptive immune responses. The inflammatory responses induced by TLRs play an important role TLRs not only in host defense from infection, but also in tissue repair and regeneration. This latter function of TLRs can also contribute to tumorigenesis. Here we review recent progress in understanding the role of TLRs in cancer development.     

Toll-like receptors and innate immunity

Toll-like receptors (TLRs) are evolutionarily conserved innate receptors expressed in various immune and non-immune cells of the mammalian host. TLRs play a crucial role in defending against pathogenic microbial infection through the induction of inflammatory cytokines and type I interferons. Furthermore, TLRs also play roles in shaping pathogen-specific humoral and cellular adaptive immune responses. In this review, we describe the recent advances in pathogen recognition by TLRs and TLR signaling.     

Toll-like receptors signaling in glomerular diseases

Abstract

Toll-like receptors (TLRs) are pattern-recognition receptors that recognize microbial/vial-derived components that trigger innate immune response, which indicate these molecules play a role in host defense against infection. The infection often precedes numerous disorders including glomerular diseases (glomerulonephritis (GN)). It is reported that TLRs are also involved in the risk and progression of GN, and TLRs may be potential therapeutic targets for GN. To date, a number of studies have found that TLRs are involved in the pathogenesis of GN. There is a paucity of reviews in the literature discussing signaling pathways and gene expression for TLRs in GN. This review was performed to provide a relatively complete signaling pathway flowchart for TLRs to the investigators who were interested in the roles of TLRs in the pathogenesis of GN. In the past decades, some studies were also performed to explore the association of TLRs gene expression with the risk of GN. However, the role of TLRs in the pathogenesis of GN remains controversial. Here, the signal transduction pathways of TLRs and its role of gene expression in the pathogenesis of GN were reviewed.     

Tissue expression of Toll-like receptors 2 and 4 in sporadic human colorectal cancer

Background  

Toll-like receptors (TLRs) play an important role in innate immunity by sensing a variety of pathogens and inducing acquired immunity. To test our hypothesis that dysregulation of innate immune responses acts to trigger carcinogenesis, we studied the expression of TLR2 and 4 in sporadic human colorectal cancer tissue.     

Toll-like receptor signaling: a perspective to develop vaccine against leishmaniasis

The toll-like receptors (TLRs) are the sentinel factor of the innate immunity, which are essential for host defense. These receptors detect the presence of conserved molecular patterns of potentially pathogenic microorganisms and contribute in both, cellular as well as humoral immune responses. Leishmania is an intracellular pathogen that silently invades host immune system. After phagocytosis, it divides and proliferates in the harmful environment of host macrophages by down-regulating its vital effector functions. In leishmaniasis, the outcome of the infection basically relies on the skewed balance between Th1/Th2 immune responses. Lots of work have been done and on progress but still characterization of either preventive or prophylactic candidate antigen/s is far from satisfactory. How does Leishmania regulate host innate immune system? Still it is unanswered. TLRs play very important role during inflammatory process of various diseases such as cancer, bacterial and viral infections but TLR signaling is comparatively less explained in leishmanial infection. In the context to Th1/Th2 dichotomy, identification of leishmanial antigens that modulate toll-like receptor signaling will certainly help in the development of future vaccine. This review will initially describe global properties of TLRs, and later will discuss their role in the pathogenesis of leishmaniasis.     

Toll样受体与树突状细胞介导的天然免疫和获得性免疫

树突状细胞(dendritic cells,DCs)作为迄今所发现的抗原提呈功能最强的一类抗原提呈细胞,是联结天然免疫和获得性免疫的桥梁。Toll样受体(Toll-like receptors,TLRs)是一类进化保守的胚系编码的模式识别受体,在DCs的抗原识别、递呈及激活T细胞等方面具有重要作用,是机体受外来抗原入侵后作出适当免疫反应的调控点。现就TLRs在不同DCs亚群中的分布、与DCs介导的天然免疫和获得性免疫的关系及DCs功能可塑性的分子基础作一综述。     

The circular RNA circBCL2L1 regulates innate immune responses via microRNA-mediated downregulation of TRAF6 in teleost fish

Growing numbers of studies have shown that circular RNAs (circRNAs) can function as regulatory factors to regulate the innate immune response, cell proliferation, cell migration, and other important processes in mammals. However, the function and regulatory mechanism of circRNAs in lower vertebrates are still unclear. Here, we discovered a novel circRNA derived from the gene encoding Bcl-2-like protein 1 (BCL2L1) gene, named circBCL2L1, which was related to the innate immune responses in teleost fish. Results indicated that circBCL2L1 played essential roles in host antiviral immunity and antibacterial immunity. Our study also identified a microRNA, miR-30c-3-3p, which could inhibit the innate immune response by targeting inflammatory mediator TRAF6. And TRAF6 is a key signal transduction factor in innate immune response mediated by TLRs. Moreover, we also found that the antiviral and antibacterial effects inhibited by miR-30c-3-3p could be reversed with the expression of circBCL2L1. Our data revealed that circBCL2L1 functioned as a competing endogenous RNA (ceRNA) of TRAF6 by competing for binding with miR-30c-3-3p, leading to activation of the NF-κB/IRF3 inflammatory pathway and then enhancing the innate immune responses. Our results suggest that circRNAs can play an important role in the innate immune response of teleost fish.     

Differential roles for RIG-I-like receptors and nucleic acid-sensing TLR pathways in controlling a chronic viral infection

The necessity for pathogen recognition of viral infection by the innate immune system in initiating early innate and adaptive host defenses is well documented. However, little is known about the role these receptors play in the maintenance of adaptive immune responses and their contribution to resolution of persistent viral infections. In this study, we demonstrate a nonredundant functional requirement for both nucleic acid-sensing TLRs and RIG-I-like receptors in the control of a mouse model of chronic viral infection. Whereas the RIG-I-like receptor pathway was important for production of type I IFNs and optimal CD8(+) T cell responses, nucleic acid-sensing TLRs were largely dispensable. In contrast, optimal anti-viral Ab responses required intact signaling through nucleic acid-sensing TLRs, and the absence of this pathway correlated with less virus-specific Ab and deficient long-term virus control of a chronic infection. Surprisingly, absence of the TLR pathway had only modest effects on Ab production in an acute infection with a closely related virus strain, suggesting that persistent TLR stimulation may be necessary for optimal Ab responses in a chronic infection. These results indicate that innate virus recognition pathways may play critical roles in the outcome of chronic viral infections through distinct mechanisms.     

The relationship between SNPS in the genes of TLR signal transduction pathway downstream elements and rheumatoid arthritis susceptibility

Toll-like receptors (TLRs) play an important role in the induction and regulation of the innate immune system or adaptive immune responses. Genetic variations within human TLRs have been reported to be associated with rheumatoid arthritis (RA). This study was conducted to investigate correlation between SNP of downstream mononucleotide in signal transduction of Toll-like receptors and predisposing genes of RA. There was obviously correlative between single nucleotide polymorphism and predisposing genes of RA. G-type of IL-1RAP rs766442 may be protecting genes of RA, while T-type alleles of IL-6R rs11265618 and IL-1RAP rs766442 may be susceptible genes of RA. In conclusion, the studies on the nucleis acid polymorphism in TLRs signal pathway contribute to disclose genes’ influence on the attack mechanism of RA, early diagnosis and treatment of RA.     

Toll‐like receptors in prostate infection and cancer between bench and bedside

Toll‐Like receptors (TLRs) are a family of evolutionary conserved transmembrane proteins that recognize highly conserved molecules in pathogens. TLR‐expressing cells represent the first line of defence sensing pathogen invasion, triggering innate immune responses and subsequently priming antigen‐specific adaptive immunity. In vitro and in vivo studies on experimental cancer models have shown both anti‐ and pro‐tumoural activity of different TLRs in prostate cancer, indicating these receptors as potential targets for cancer therapy. In this review, we highlight the intriguing duplicity of TLR stimulation by pathogens: their protective role in cases of acute infections, and conversely their negative role in favouring hyperplasia and/or cancer onset, in cases of chronic infections. This review focuses on the role of TLRs in the pathophysiology of prostate infection and cancer by exploring the biological bases of the strict relation between TLRs and prostate cancer. In particular, we highlight the debated question of how reliable mutations or deregulated expression of TLRs are as novel diagnostic or prognostic tools for prostate cancer. So far, the anticancer activity of numerous TLR ligands has been evaluated in clinical trials only in organs other than the prostate. Here we review recent clinical trials based on the most promising TLR agonists in oncology, envisaging a potential application also in prostate cancer therapy.     

Toll-like receptor 3 upregulation in macrophages participates in the initiation and maintenance of pristane-induced arthritis in rats

Introduction  

Toll-like receptors (TLRs) are involved in both innate and adaptive immune responses and are likely to play a complex role in the pathogenesis of human rheumatoid arthritis (RA) and experimental arthritis. The objective of this study was to identify the key TLR in pristane-induced arthritis (PIA), a rat model for RA, and to clarify its roles in the initiation and maintenance of arthritis.     

TLR family and viral infection

The immune system has been divided into innate and adaptive component, each of which has different roles and functions in defending the organism against foreign agents, such as bacteria and viruses. An important advance in our understanding of early events in microbial recognition and subsequent development of immune responses was the identification of Toll-like receptors (TLRs) as key molecules of the innate immune systems. The family of TLRs in vertebrates detects conserved structures found in a broad range of pathogens and triggers innate immune responses. At present, 11 members of the TLR family have been identified. A subset of TLRs recognize viral components and induce antiviral responses by producing type I interferons. Recent accumulating evidence has clarified signaling pathways triggered by TLRs in viral infection.     

Blocking monoclonal antibodies of TIM proteins as orchestrators of anti-tumor immune response

Monoclonal antibody (mAb)-based treatment of cancer has a significant effect on current practice in medical oncology, and is considered now as one of the most successful therapeutic strategies for cancer treatment. MAbs are designed to initiate or enhance anti-tumor immune responses, which can be achieved by either blocking inhibitory immune checkpoint molecules or triggering activating receptors. TIM gene family members are type-I surface molecules expressed in immune cells, and play important roles in the regulation of both innate and adaptive arms of the immune system. Therapeutic strategies based on anti-TIMs mAbs have shown promising results in experimental tumor models, and synergistic combinations of anti-TIMs mAbs with cancer vaccines, adoptive T-cell therapy, radiotherapy and chemotherapy will have great impact on cancer treatment in future clinical development.     

Blocking monoclonal antibodies of TIM proteins as orchestrators of anti-tumor immune response

Monoclonal antibody (mAb)-based treatment of cancer has a significant effect on current practice in medical oncology, and is considered now as one of the most successful therapeutic strategies for cancer treatment. MAbs are designed to initiate or enhance anti-tumor immune responses, which can be achieved by either blocking inhibitory immune checkpoint molecules or triggering activating receptors. TIM gene family members are type-I surface molecules expressed in immune cells, and play important roles in the regulation of both innate and adaptive arms of the immune system. Therapeutic strategies based on anti-TIMs mAbs have shown promising results in experimental tumor models, and synergistic combinations of anti-TIMs mAbs with cancer vaccines, adoptive T-cell therapy, radiotherapy and chemotherapy will have great impact on cancer treatment in future clinical development.     

Toll-like receptors and their role in animal reproduction

Toll-like receptors (TLRs) are evolutionarily conserved innate immune receptors that recognize pathogen specific molecular pattern (PAMPs) in an efficient, non-self-reactive manner and initiate specific immune signaling that culminates in triggering antigen-specific adaptive responses. Different TLR genes in domestic animal species have been characterized and accumulating evidence from recent studies indicates an extended role for TLR signaling in reproductive physiology. In females, TLRs have been implicated in the regulation of ovulation, fertilization, gestation and parturition, as well as in pathological conditions such as endometritis and mastitis. In males, TLRs play a role in steroidogenesis and spermatogenesis. Use of TLR agonists has also been shown to be effective in the treatment of certain reproductive tract infections. Moreover, gene polymorphisms in TLRs have been associated with mastitis providing evidence that TLRs can potentially be exploited as markers in future breeding programs. The aim of this review is to provide a comprehensive treatise on role of TLRs in male and female reproductive physiology and associated pathology in domestic livestock.     

Nucleic acid-sensing TLRs as modifiers of autoimmunity

The immune system requires precise regulation of activating and inhibitory signals so that it can mount effective responses against pathogens while ensuring tolerance to self-components. Some of the most potent activation signals are triggered by innate immune molecules, particularly those in the TLR family. Recent studies have shown that engagement of TLRs plays a significant role in both innate and adaptive immunity. This review focuses on the ways that TLR function might contribute to the etiology of lupus-like syndromes in the context of an autoimmune-prone environment. By considering the sources, localization, and expression of both nucleic acids and the molecules that bind them, we discuss several ways that innate immunity can play a role in the development of systemic autoimmunity.     

Toll-like receptors and intestinal defence: molecular basis and therapeutic implications

Toll-like receptors (TLRs) play a principle role in distinct pathogen recognition and in the initiation of innate immune responses of the intestinal mucosa. Activated innate immunity interconnects downstream with adaptive immunity in complex feedback regulatory loops. Intestinal disease might result from inappropriate activation of the mucosal immune system driven by TLRs in response to normal luminal flora.