Toll-like receptors (TLRs) are pattern recognition receptors (PRRs) expressed in a wide spectrum of cell types that recognize distinctive ligands and subsequently activate adaptive immune responses. TLR ligands are considered a promising target for development of immunomodulatory agents. Extensive clinical investigations are currently underway to develop TLR ligands-based non-specific immunostimulants and vaccine adjuvants. It has been well accepted that cancer cells develop a strategy to avoid host immune responses by producing inhibitory molecules. In addition, tumor-associated antigens are often not strong enough to induce effective anti-cancer immune responses. In this context, immunostimulants or adjuvants are critically required for more effective cancer immunotherapies. Here, we discuss recent progresses in the field of cancer immunotherapy under special emphasis on the TLR ligands as a component of immunostimulatory agents.
Adjuvants, Immunologic ; Immunotherapy ; Ligands ; Receptors, Pattern Recognition ; Toll-Like Receptors

Chronic rhinosinusitis (CRS) is a multifactorial and heterogeneous disease, and variousfactors, such as inflammation, infection, fungus, and superantigens, have been proposed to play crucial roles in its pathogenesis. Recently, the dominant mechanismof CRS pathogenesis has shiftedfrom microbial infection and environmental factors to host susceptibility. Host susceptibility relies not only on adaptive immunity, but also on innate immunity, and there has recently been much research into innate immunity. Innate immunity is an evolutionally conserved immune system that recognizes microbial signature molecules via pattern recognition receptors and is a primary defense system that elicits inflammatory and bactericidal responses. Dysfunction of the host response to pathogens is suggested to be involved in pathogenesis of CRS and an irrelevant response of the host's innate immunity could cause a failure toeradicate the pathogens, thereby contributing to CRS pathogeneses. Among these innate immune systems, toll-like receptors and epithelial barrier functions have been studied extensively, and new players, such as innate lymphoid cells,have beensurfacing. Betterunderstanding of innate immunity couldhelp to investigateand treat this complex disease. In this review, toll-like receptors, epithelial barrier functions, and innate lymphoid cells,among many subjects related to innate immunity,will be discussed in terms of pathogenesis.
Adaptive Immunity ; Fungi ; Immune System ; Immunity, Innate* ; Inflammation ; Receptors, Pattern Recognition ; Superantigens ; Toll-Like Receptors

Detection of pathogen by pattern recognition receptors leads to activation of inflammasome which plays a crucial role in immune system. The inflammasome regulates the release of cytokines, such as interleukin (IL)-1beta, IL-18 and high-mobility group box 1 (HMGB1). Double-stranded RNA-dependent protein kinase (PKR) is a critical component of an inflammatory complex. Recently, the critical role of PKR was reported in regulation of multiple inflammasomes.
Cytokines ; eIF-2 Kinase ; Immune System ; Inflammasomes ; Interleukin-18 ; Interleukins ; Receptors, Pattern Recognition

Inflammation is an immune response mediated by innate immune cells of tissues, against invading microbes and cellular stress. The hallmark of inflammatory responses is the activation of inflammasomes — multiprotein oligomers comprising intracellular pattern recognition receptors and inflammatory effectors — such as ASC and pro-cysteine-aspartic protease (pro-caspase)-1. Inflammasomes can be classified as canonical or non-canonical, and their activation in response to various ligands commonly induces caspase-1 activation and gasdermin D (GSDMD) processing, leading to caspase-1-mediated maturation and secretion of the pro-inflammatory cytokines IL-1β and IL-18, and GSDMD-mediated pyroptosis through pore generation in cell membranes. Although inflammation protects the host from harmful stimuli, chronic inflammation is a critical risk factor for inflammatory diseases, and several studies have investigated the role of canonical inflammasomes in inflammatory responses and diseases, with emerging studies focusing on the role of non-canonical inflammasomes. This review discusses recent studies on the regulatory roles of the caspase-11 non-canonical inflammasome in the pathogenesis of inflammatory diseases. Additionally, it provides an insight into the development of novel therapeutics based on targeting caspase-11 non-canonical inflammasome and its downstream effectors to prevent and treat human inflammatory conditions.
Cell Membrane ; Cytokines ; Humans ; Inflammasomes* ; Inflammation ; Interleukin-18 ; Ligands ; Pyroptosis ; Receptors, Pattern Recognition ; Risk Factors

DNA sensor, a kind of pattern recognition receptor (PRR), is widely expressed in innate immune cells. It activates the inflammatory signaling pathways and triggers an innate immune response by recognizing the pathogens or DNA in abnormal host cells. DNA-dependent activator of IFN-regulatory factors (DAI) is the first cytoplasmic DNA receptor discovered, which plays an important role in regulating the innate immune responses characterized by induction of interferon and programmed cell death. The article summarizes the molecular characteristics of DAI, its downstream signaling pathways, and its role and mechanism in anti-infective immunity, tumor immunity and inflammatory diseases. It also makes a preliminary exploration of the correlation between DAI and transplantation immunology, and provides a new target for the therapy of various immune diseases.
DNA/metabolism* ; Receptors, Pattern Recognition ; Immunity, Innate ; Signal Transduction/genetics* ; DNA-Binding Proteins/genetics*

Type 1 Interferons (T1 IFN) play a pivotal role in innate immune responses against viral infection. Recently, this anti-viral cytokines are shown to be induced during bacterial infections via activation of various pattern recognition receptors (PRRs) including Toll-like receptors, RIG-I-like receptors, or NOD-like receptors. Signaling mediators such as MyD88, TRIF, MAVS, STING, or RIP2 of the receptor signaling pathways are also involved in T1 IFN responses depending on the bacterial species and their ligands. However, role of T1 IFN in anti-bacterial immunity is still obscure and its effect on immunological pathogenesis during bacterial infection has been controversial. It has been reported that T1 IFN could provide protective effect on several bacterial infections but it also aggravates pathogenic situation during some intracellular pathogens or secondary bacterial infection after respiratory viral infection. Here, we summarize recent findings how T1 IFN is induced by various bacterial pathogens and discuss the potential effect of T1 IFN responses on immune responses against bacterial infection.
Bacterial Infections* ; Bites and Stings ; Cytokines ; Immunity, Innate ; Interferon Type I* ; Interferons ; Ligands ; Receptors, Pattern Recognition ; Signal Transduction ; Toll-Like Receptors

Toll-like receptors (TLR) are well-characterized pattern recognition receptors that can recognize and respond to diverse pathogen-associated or danger-associated molecular patterns during infection. TLR signaling in macrophages triggers in the intracellular signaling pathways through the recruitment of various adaptor and signaling proteins, and results in the activation of effector mechanisms and pathways that are important for host defense to intracellular bacteria. Effector mechanisms include inflammatory responses, cytokine generation, production of reactive oxygen species, and antimicrobial proteins. Accumulating studies showed that autophagy is a key pathway in the maintenance of homeostasis and housekeeping functions during infection and inflammation. In this review, we summarize the major effector pathways and mechanisms in the activation of TLR-inducible innate immune responses in macrophages. In addition, we focus the emerging evidence of crosstalk between autophagy and TLR-mediated signaling in terms of effector function of innate immune responses. A better understanding of effector functions by the activation of TLR-mediated signaling cascades contributes to the development of new therapeutics and vaccines against various intracellular pathogenic infections.
Autophagy ; Bacteria ; Homeostasis ; Housekeeping ; Immunity, Innate ; Inflammation ; Macrophages ; Reactive Oxygen Species ; Receptors, Pattern Recognition ; Toll-Like Receptors ; Vaccines

The cockroach represents one of the most common sources of indoor allergens worldwide, and 40%-60% of patients with asthma in urban and inner-city areas possess IgE antibodies to cockroach allergens. In Korean homes, four cockroach species have been found, of which the most commonly encountered is the German cockroach. The pathogenic mechanism underlying the association between cockroach allergens and allergic diseases has not been fully elucidated. Allergenicity is associated with the cockroach allergens themselves, enzymatic protease activity, and ligands for pattern recognition receptors. Although allergen-specific adaptive immune responses orchestrate the cockroach allergic response, recent data suggest that the innate immune system is also a critical contributor to pathogenesis. We review the current evidence for the demographics of cockroach exposure and sensitization, characteristics of cockroach allergens, and inflammatory responses to cockroach allergens initiated through protease-dependent pathways.
Allergens ; Antibodies ; Asthma ; Blattellidae ; Cockroaches ; Demography ; Humans ; Hypersensitivity ; Immune System ; Immunoglobulin E ; Ligands ; Receptor, PAR-2 ; Receptors, Pattern Recognition

The innate immune system confers first-line defense against various pathogens including bacteria and viruses. Early detection of invading pathogens by the host depends on a limited number of specific pattern recognition receptors (PRRs) that detect pathogen associated molecular patterns (PAMPs) and activate signal transduction cascades that lead to activation of defense mechanisms. Among those sensors, RIG-I-like receptors (RLRs) play crucial roles in the detection of viruses by recognizing intracellular viral patterns such as viral RNAs to induce type-I interferon production. The discovery of intracellular RNA sensing mechanism by RIG-I prompted the investigations to find out intracellular DNA sensors. Recently, several proteins including DAI, AIM2, IFI16, and cGAS have been suggested as DNA sensing molecules to detect DNA viruses and bacteria, suggesting there are multiple receptors for microbial DNA. In this review, we discuss the current our understanding of sensing microbial DNA and subsequent induction of immune responses.
Bacteria ; Defense Mechanisms ; DNA ; DNA Viruses ; Immune System ; Immunity, Innate ; Interferons ; Proteins ; Receptors, Pattern Recognition ; RNA ; RNA, Viral ; Signal Transduction

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that bridge innate and adaptive immune responses, thereby leading to immune activation. DCs have been known to recognize pathogen-associated molecular patterns such as lipopolysaccharides (LPS) and nucleic acids via their pattern recognition receptors, which trigger signaling of their maturation and effector functions. Furthermore, DCs take up and process antigens as a form of peptide loaded on the major histocompatibility complex (MHC) and present them to T cells, which are responsible for the adaptive immune response. Conversely, DCs can also play a role in inducing immune suppression under specific circumstances. From this perspective, the role of DCs is related to tolerance rather than immunity. Immunologists refer to these special DCs as tolerogenic DCs (tolDCs). However, the definition of tolDCs is controversial, and there is limited information on their development and characteristics. In this review, we discuss the current concept of tolDCs, cutting-edge methods for generating tolDCs in vitro, and future applications of tolDCs, including clinical use.
Adaptive Immunity ; Antigen-Presenting Cells ; Dendritic Cells* ; Lipopolysaccharides ; Major Histocompatibility Complex ; Nucleic Acids ; Receptors, Pattern Recognition ; T-Lymphocytes