Toll-like receptors: function and roles in lung disease

2004 ◽  
Vol 286 (5) ◽  
pp. L887-L892 ◽  
Author(s):  
Subhendu Basu ◽  
Matthew J. Fenton
Keyword(s):  
Immune Responses ◽  
Allergic Asthma ◽  
Lung Diseases ◽  
Protective Role ◽  
Airway Hyperreactivity ◽  
Toll Like Receptor ◽  
Adaptive Immune ◽  
Bacterial Lipopolysaccharides ◽  
Molecular Patterns

Toll-like receptor (TLR) proteins have been shown to play a pivotal role in both innate and adaptive immune responses in higher vertebrates. TLR proteins enable the host to recognize a large number of pathogen-associated molecular patterns such as bacterial lipopolysaccharides, viral RNA, CpG-containing DNA, and flagellin, among others. Engagement of TLR proteins leads to the upregulation of costimulatory molecules and proinflammatory cytokines, as well as reactive nitrogen and oxygen products. The role of TLR proteins in lung-associated pathologies such as airway hyperreactivity, allergic asthma, and tuberculosis is being intensively studied. This review summarizes many of the findings made to date on the roles of TLR proteins in a variety of lung diseases. Generally, TLR proteins serve a protective role in infectious diseases, such as tuberculosis. The progression of chronic inflammatory lung diseases, such as allergic asthma, can also be influenced by TLR-dependent responses.

scholarly journals The Immune Response toTrypanosoma cruzi: Role of Toll-Like Receptors and Perspectives for Vaccine Development

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Mauricio M. Rodrigues ◽  
Ana Carolina Oliveira ◽  
Maria Bellio
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Vaccine Development ◽  
State Of The Art ◽  
Toll Like Receptor ◽  
Vaccine Research ◽  
The Past ◽  
Acquired Immune Responses ◽  
Molecular Patterns

In the past ten years, studies have shown the recognition ofTrypanosoma cruzi-associated molecular patterns by members of the Toll-like receptor (TLR) family and demonstrated the crucial participation of different TLRs during the experimental infection with this parasite. In the present review, we will focus on the role of TLR-activated pathways in the modulation of both innate and acquired immune responses toT. cruziinfection, as well as discuss the state of the art of vaccine research and development against the causative agent of Chagas disease (or American trypanosomiasis).

scholarly journals Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis

2006 ◽  
Vol 175 (2) ◽  
pp. 209-215 ◽  
Author(s):  
Yinghua Ma ◽  
Jianxue Li ◽  
Isaac Chiu ◽  
Yawen Wang ◽  
Jacob A. Sloane ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neurite Outgrowth ◽  
Cortical Neurons ◽  
Neuronal Apoptosis ◽  
Negative Regulator ◽  
Toll Like Receptor ◽  
Neuronal Responses ◽  
Adaptive Immune ◽  
Cultured Cortical Neurons

Toll receptors in Drosophila melanogaster function in morphogenesis and host defense. Mammalian orthologues of Toll, the Toll-like receptors (TLRs), have been studied extensively for their essential functions in controlling innate and adaptive immune responses. We report that TLR8 is dynamically expressed during mouse brain development and localizes to neurons and axons. Agonist stimulation of TLR8 in cultured cortical neurons causes inhibition of neurite outgrowth and induces apoptosis in a dissociable manner. Our evidence indicates that such TLR8-mediated neuronal responses do not involve the canonical TLR–NF-κB signaling pathway. These findings reveal novel functions for TLR8 in the mammalian nervous system that are distinct from the classical role of TLRs in immunity.

scholarly journals The Role of Macrophages in the Development of Acute and Chronic Inflammatory Lung Diseases

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 897
Author(s):  
Jae-Won Lee ◽  
Wanjoo Chun ◽  
Hee Jae Lee ◽  
Jae-Hong Min ◽  
Seong-Man Kim ◽  
...  
Keyword(s):  
Allergic Asthma ◽  
Lung Diseases ◽  
Inflammatory Responses ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Adaptive Immune ◽  
Activation Of Transcription ◽  
Organ Systems ◽  
Underlying Mechanisms

Macrophages play an important role in the innate and adaptive immune responses of organ systems, including the lungs, to particles and pathogens. Cumulative results show that macrophages contribute to the development and progression of acute or chronic inflammatory responses through the secretion of inflammatory cytokines/chemokines and the activation of transcription factors in the pathogenesis of inflammatory lung diseases, such as acute lung injury (ALI), acute respiratory distress syndrome (ARDS), ARDS related to COVID-19 (coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), allergic asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). This review summarizes the functions of macrophages and their associated underlying mechanisms in the development of ALI, ARDS, COVID-19-related ARDS, allergic asthma, COPD, and IPF and briefly introduces the acute and chronic experimental animal models. Thus, this review suggests an effective therapeutic approach that focuses on the regulation of macrophage function in the context of inflammatory lung diseases.

scholarly journals Precision N-Glycoproteomic Profiling of Murine Peritoneal Macrophages After Different Stimulations

2021 ◽  
Vol 12 ◽  
Author(s):  
Lujie Yang ◽  
Tianqi Gong ◽  
Huali Shen ◽  
Jiangnan Pei ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Macrophage Activation ◽  
Cytokine Production ◽  
Peritoneal Macrophages ◽  
Biological Processes ◽  
Toll Like Receptor ◽  
Adaptive Immune ◽  
Murine Peritoneal Macrophages ◽  
Molecular Patterns ◽  
Stimulation Of

Macrophages are important immune cells that participate in both innate and adaptive immune responses, such as phagocytosis, recognition of molecular patterns, and activation of the immune response. In this study, murine peritoneal macrophages were isolated and then activated by LPS, HSV and VSV. Integrative proteomic and precision N-glycoproteomic profiling were conducted to assess the underlying macrophage activation. We identified a total of 587 glycoproteins, including 1239 glycopeptides, 526 monosaccharide components, and 8326 intact glycopeptides in glycoproteomics, as well as a total of 4496 proteins identified in proteomic analysis. These glycoproteins are widely involved in important biological processes, such as antigen presentation, cytokine production and glycosylation progression. Under the stimulation of the different pathogens, glycoproteins showed a dramatic change. We found that receptors in the Toll-like receptor pathway, such as Tlr2 and CD14, were increased under LPS and HSV stimulation. Glycosylation of those proteins was proven to influence their subcellular locations.

scholarly journals Holding the Inflammatory System in Check: TLRs and Their Targeted Therapy in Asthma

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Zhiyong Dong ◽  
Lingxin Xiong ◽  
Weijie Zhang ◽  
Peter G. Gibson ◽  
Ting Wang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Biological Response ◽  
Protective Role ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Pathogenic Factors ◽  
Genetic And Environmental Factors ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Inflammatory System

Inflammation is a complex biological response to detrimental stimuli and can be a double-edged sword. Inflammation plays a protective role in removing pathogenic factors, but dysregulated inflammation is associated with several major fatal diseases such as asthma, cancer, and cardiovascular diseases. Asthma is a complex heterogenous disease caused by genetic and environmental factors. TLRs are the primary proteins associated with the innate and adaptive immune responses to these fatal factors and play an important role in recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), which initiates the downstream immune response. Due to the complex TLRs cascade and nowadays unsuccessful control in asthma, new studies are focused on TLRs and other potential targets in TLR cascade to minimize airway inflammation.

scholarly journals Role of the Innate Immunity Signaling Pathway in the Pathogenesis of Sjögren’s Syndrome

2021 ◽  
Vol 22 (6) ◽  
pp. 3090
Author(s):  
Toshimasa Shimizu ◽  
Hideki Nakamura ◽  
Atsushi Kawakami
Keyword(s):  
Immune Responses ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Innate Immune ◽  
Type I ◽  
Type I Ifn ◽  
Adaptive Immune ◽  
Sjögren‘S Syndrome

Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by chronic inflammation of the salivary and lacrimal glands and extra-glandular lesions. Adaptive immune response including T- and B-cell activation contributes to the development of SS. However, its pathogenesis has not yet been elucidated. In addition, several patients with SS present with the type I interferon (IFN) signature, which is the upregulation of the IFN-stimulated genes induced by type I IFN. Thus, innate immune responses including type I IFN activity are associated with SS pathogenesis. Recent studies have revealed the presence of activation pattern recognition receptors (PRRs) including Toll-like receptors, RNA sensor retinoic acid-inducible gene I and melanoma differentiation-associated gene 5, and inflammasomes in infiltrating and epithelial cells of the salivary glands among patients with SS. In addition, the activation of PRRs via the downstream pathway such as the type I IFN signature and nuclear factor kappa B can directly cause organ inflammation, and it is correlated with the activation of adaptive immune responses. Therefore, this study assessed the role of the innate immune signal pathway in the development of inflammation and immune abnormalities in SS.

scholarly journals The Role of Macrophages in the Host’s Defense against Sporothrix schenckii

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 905
Author(s):  
Estela Ruiz-Baca ◽  
Armando Pérez-Torres ◽  
Yolanda Romo-Lozano ◽  
Daniel Cervantes-García ◽  
Carlos A. Alba-Fierro ◽  
...  
Keyword(s):  
Immune Responses ◽  
Macrophage Polarization ◽  
Sporothrix Schenckii ◽  
Macrophage Cell ◽  
Cell Recruitment ◽  
Host Pathogen Interaction ◽  
Interaction Processes ◽  
Host Pathogen ◽  
Molecular Patterns

The role of immune cells associated with sporotrichosis caused by Sporothrix schenckii is not yet fully clarified. Macrophages through pattern recognition receptors (PRRs) can recognize pathogen-associated molecular patterns (PAMPs) of Sporothrix, engulf it, activate respiratory burst, and secrete pro-inflammatory or anti-inflammatory biological mediators to control infection. It is important to consider that the characteristics associated with S. schenckii and/or the host may influence macrophage polarization (M1/M2), cell recruitment, and the type of immune response (1, 2, and 17). Currently, with the use of new monocyte-macrophage cell lines, it is possible to evaluate different host–pathogen interaction processes, which allows for the proposal of new mechanisms in human sporotrichosis. Therefore, in order to contribute to the understanding of these host–pathogen interactions, the aim of this review is to summarize and discuss the immune responses induced by macrophage-S. schenckii interactions, as well as the PRRs and PAMPs involved during the recognition of S. schenckii that favor the immune evasion by the fungus.

scholarly journals Essential role of IRAK-4 protein and its kinase activity in Toll-like receptor–mediated immune responses but not in TCR signaling

2007 ◽  
Vol 204 (5) ◽  
pp. 1013-1024 ◽  
Author(s):  
Tatsukata Kawagoe ◽  
Shintaro Sato ◽  
Andreas Jung ◽  
Masahiro Yamamoto ◽  
Kosuke Matsui ◽  
...  
Keyword(s):  
Immune Responses ◽  
Kinase Activity ◽  
Interleukin 1 ◽  
Cell Receptor ◽  
Nuclear Factor Κb ◽  
Toll Like Receptor ◽  
Tcr Signaling ◽  
Mitogen Activated Protein

Interleukin-1 receptor–associated kinase 4 (IRAK-4) was reported to be essential for the Toll-like receptor (TLR)– and T cell receptor (TCR)–mediated signaling leading to the activation of nuclear factor κB (NF-κB). However, the importance of kinase activity of IRAK family members is unclear. In this study, we investigated the functional role of IRAK-4 activity in vivo by generating mice carrying a knockin mutation (KK213AA) that abrogates its kinase activity. IRAK-4KN/KN mice were highly resistant to TLR-induced shock response. The cytokine production in response to TLR ligands was severely impaired in IRAK-4KN/KN as well as IRAK-4−/− macrophages. The IRAK-4 activity was essential for the activation of signaling pathways leading to mitogen-activated protein kinases. TLR-induced IRAK-4/IRAK-1–dependent and –independent pathways were involved in early induction of NF-κB–regulated genes in response to TLR ligands such as tumor necrosis factor α and IκBζ. In contrast to a previous paper (Suzuki, N., S. Suzuki, D.G. Millar, M. Unno, H. Hara, T. Calzascia, S. Yamasaki, T. Yokosuka, N.J. Chen, A.R. Elford, et al. 2006. Science. 311:1927–1932), the TCR signaling was not impaired in IRAK-4−/− and IRAK-4KN/KN mice. Thus, the kinase activity of IRAK-4 is essential for the regulation of TLR-mediated innate immune responses.

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