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.

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 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 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.

scholarly journals ATP Induces IL-1βSecretion inNeisseria gonorrhoeae-Infected Human Macrophages by a Mechanism Not Related to the NLRP3/ASC/Caspase-1 Axis

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Killen García ◽  
Gisselle Escobar ◽  
Pablo Mendoza ◽  
Caroll Beltran ◽  
Claudio Perez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Evasion ◽  
Transcriptional Activation ◽  
Pore Formation ◽  
Human Monocyte ◽  
Positive Staining ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Caspase 1

Neisseria gonorrhoeae(Ngo) has developed multiple immune evasion mechanisms involving the innate and adaptive immune responses. Recent findings have reported that Ngo reduces the IL-1βsecretion of infected human monocyte-derived macrophages (MDM). Here, we investigate the role of adenosine triphosphate (ATP) in production and release of IL-1βin Ngo-infected MDM. We found that the exposure of Ngo-infected MDM to ATP increases IL-1βlevels about ten times compared with unexposed Ngo-infected MDM (P<0.01). However, we did not observe any changes in inflammasome transcriptional activation of speck-like protein containing a caspase recruitment domain (CARD) (ASC,P>0.05) and caspase-1 (CASP1,P>0.05). In addition, ATP was not able to modify caspase-1 activity in Ngo-infected MDM but was able to increase pyroptosis (P>0.01). Notably ATP treatment defined an increase of positive staining for IL-1βwith a distinctive intracellular pattern of distribution. Collectively, these data demonstrate that ATP induces IL-1βsecretion by a mechanism not related to the NLRP3/ASC/caspase-1 axis and likely is acting at the level of vesicle trafficking or pore formation.

Role of DAP12 in Innate and Adaptive Immune Responses

2003 ◽  
Vol 9 (1) ◽  
pp. 7-10 ◽  
Author(s):  
Naoko Aoki ◽  
Shoji Kimura ◽  
Zhou Xing
Keyword(s):  
Immune Responses ◽  
Adaptive Immune Responses ◽  
Adaptive Immune

scholarly journals IL-10 produces a dual effect on OGD-induced neuronal apoptosis of cultured cortical neurons via the NF-κB pathway

Aging ◽  
2019 ◽  
Vol 11 (23) ◽  
pp. 10796-10813 ◽  
Author(s):  
Hongbin Chen ◽  
Wei Lin ◽  
Peiqiang Lin ◽  
Mouwei Zheng ◽  
Yongxing Lai ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Neuronal Apoptosis ◽  
Dual Effect ◽  
Cultured Cortical Neurons
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