Toll-like Receptors In Immune Response Research Articles

The Emerging Role of Toll-Like Receptor-Mediated Neuroinflammatory Signals in Psychiatric Disorders and Acquired Epilepsy.

The new and evolving paradigms of psychiatric disorders pathogenesis are deeply inclined toward chronic inflammation that leads to disturbances in the neuronal networks of patients. A strong association has been established between the inflammation and neurobiology of depression which is mediated by different toll-like receptors (TLRs). TLRs and associated signalling pathways are identified as key immune regulators to stress and infections in neurobiology. They are a special class of transmembrane proteins, which are one of the broadly studied members of the Pattern Recognition Patterns family. This review focuses on summarizing the important findings on the role of TLRs associated with psychotic disorders and acquired epilepsy. This review also shows the promising potential of TLRs in immune response mediated through antidepressant therapies and TLRs polymorphism associated with various psychotic disorders. Moreover, this also sheds light on future directions to further target TLRs as a therapeutic approach for psychiatric disorders.

Current Understanding of the Innate Control of Toll-like Receptors in Response to SARS-CoV-2 Infection.

The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, threatens the entire world. It has affected every aspect of life and increased the burden on both healthcare and socioeconomic systems. Current studies have revealed that excessive inflammatory immune responses are responsible for the severity of COVID-19, which suggests that anti-inflammatory drugs may be promising therapeutic treatments. However, there are currently a limited number of approved therapeutics for COVID-19. Toll-like receptors (TLRs), which recognize microbial components derived from invading pathogens, are involved in both the initiation of innate responses against SARS-CoV-2 infection and the hyperinflammatory phenotype of COVID-19. In this review, we provide current knowledge on the pivotal role of TLRs in immune responses against SARS-CoV-2 infection and demonstrate the potential effectiveness of TLR-targeting drugs on the control of hyperinflammation in patients with COVID-19.

TLR stimulation of human neutrophils lead to increased release of MCP-1, MIP-1α, IL-1β, IL-8 and TNF during tuberculosis

Neutrophils inform and shape immune responses. Toll-like receptors (TLRs) play an essential part in the perception of microbes and shape the complex host responses that occur during infection. The TLRs present on neutrophils play an indispensable role in neutrophil mediated pathogen recognition and elimination. This study was done to identify the role of significant TLRs in immune responses leading to differences in cytokine/chemokine release following stimulation. We evaluated the concentrations of various significant cytokines (IL-1β, TNF, MIP-1α, MCP-1 and IL-8) secreted by neutrophils from healthy donors and pulmonary tuberculosis patients following TLR ligand stimulation. TLR stimulation increased the release of such cytokines in both the groups. Thus it is noted that TLR stimulation of neutrophils definitely lead to increased cytokine response. Also, the release of all the studied cytokines are found to be greatly increased in patient neutrophils, affirming that neutrophils undergo secretory level modifications during tuberculosis infection.

Outcome of Mycobacterium tuberculosis and Toll-like receptor interaction: immune response or immune evasion?

Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, is an intracellular bacterium capable of surviving and persisting within host mononuclear cells. The host response against tubercle bacilli is dominated by fine-tuned interaction of innate and adaptive immune responses. Toll-like receptors (TLRs) play a critical role in the formation of this immune response by facilitating in elaboration of protective T helper type 1 (Th1) cytokines and microbicidal molecules, but the intracellular persistence of M. tuberculosis in the phagosome and processing and presentation of TLR ligands by host antigen-presenting cell leads to continuous and chronic TLR2 signaling. The prolonged stimulation of TLR ultimately results in elaboration of immunosuppressive cytokines and downregulation of antigen presentation by major histocompatibility complex (MHC) class II and therefore becomes beneficial for M. tuberculosis, resulting in its continued survival inside macrophages. An understanding of the host-pathogen interaction in tuberculosis is important to delineate the mechanisms that can modulate the immune response toward protection. This review focuses on the role of TLRs in immune response and immune evasion and how M. tuberculosis maintains its dominance over the host during infection. A precise understanding of the TLRs and M. tuberculosis interaction will undoubtedly lead to the development of novel therapies to combat tuberculosis.

Toll‐like receptors and skin

Toll-like receptors are important pattern recognition receptors which have key roles in both innate and adaptive immune responses. They are strongly associated with the pathogenesis of inflammatory and autoimmune diseases. Furthermore, Toll-like receptors have also been implicated in the pathogenesis of several skin diseases such as skin infections, psoriasis, acne vulgaris, lichen planus, Behçet's disease, leprosy, syphilis, Lyme disease, atopic dermatitis and allergic contact dermatitis, mycosis fungoides, non-melanoma skin cancers and melanoma. In this manuscript, the structure and functions of Toll-like receptors in immune responses, their impact on skin diseases and recent advances on therapeutic usage have been reviewed.

Toll-like receptors in immune response to the viral infections

Toll-like receptors (TLRs) are members of the innate immunity system. They are responsible for the recognition of various antigens and take part in the modulation of immunity responses. In general, they are divided into "bacterial" and "viral" TLRs, even though this classification overlaps in some cases. Genetic similarity of TLRs gives them the status of highly conservative proteins throughout the animal kingdom. However, there is a certain level of variation between different species that can result in semi-disparate recognition ability. Furthermore, their universal signaling pathways predispose them not only as a target for vaccination trials in humans, but also for the genetic selection in veterinary medicine. Moreover, the selection pressure and their conservative properties make them a suitable system for the evolutionary studies, since each separate genetic system has its own unique ortholog/paralog. TLRs 2, 3, 4, 7, 8, and 9 play a crucial role in the recognition and modulation of the innate immunity in response to the viral infection due to their predominant localization on the white blood cells and endothelial cells, while intracellularly localized TLRs lead the way.

Role of Toll-Like Receptors in Immune Responses to Chlamydial Infections

Chlamydiae are important human pathogens which are leading causative agents for a variety of disease conditions including ocular, respiratory and sexually transmitted diseases, thus causing significant morbidity worldwide. Many of the human diseases caused by Chlamydia species are considered to be immunopathologically mediated. Toll like receptors (TLRs) have emerged as one of the major components of the immune system. Recognition of pathogen associated molecular patterns (PAMPs) by TLRs results in the activation of signaling events that induce the expression of effector molecules such as cytokines and chemokines which control the activation of adaptive immune responses. The precise immune mechanisms involved in resistance or pathogenesis to chlamydial infection, especially in the TLR signaling and downstream events during the innate phase of infection initiating the adaptive immune responses remains largely unknown. This review focuses on elaborating the current knowledge on the role of TLRs in immune responses to chlamydial infection. Although chlamydial components like lipopolysaccharide (LPS) and chlamydial heat shock protein 60 (cHSP60) are recognized by TLR4, the intact organisms stimulates the innate immune cells through TLR2, which also plays an important role as a PRR for Chlamydia. While the individual role of different TLRs such as TLR2, TLR4 and TLR9 in chlamydial infection is becoming delineated, studies have demonstrated the essential role of the TLR adapter molecule MyD88 in the generation of immune responses to Chlamydia infection. Given that there is no effective vaccine available for Chlamydia till date, a better understanding of the immunological and molecular mechanisms mediated by TLRs will greatly aid in possibly exploiting these molecules as immunotherapeutic targets.