Toll-like Receptor 2 in Autoimmune Inflammation

Marks, Kathryne E.; Cho, Kaylin; Stickling, Courtney; Reynolds, Joseph M.

doi:10.4110/in.2021.21.e18

Cited by 34 publications

(18 citation statements)

References 73 publications

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“… 28 TLR2, as a member of the Toll-like receptors (TLRs) family, binds the cellular components of the host, thus participated in innate immunity and serves as a bridge between innate and acquired immunity. 29 It transmits extracellular signals to activate transcription factors, such as AP-1 and nuclear factor-κB, which contributes to the production of proinflammatory cytokines and chemotactic cytokines, thus regulating the balance between Th1 cells and Th2 cells. Research finding that TLR 2, is activated and up-modulated by high mobility group box-1 (HMGB1), results in surgery-induced neuro-inflammation and impairment of memory and learning.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Immune-Related Genes and Immune Infiltration Features in Epilepsy by Multi-Transcriptome Data

Hou¹,

Chen²,

Wang³

et al. 2022

JIR

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Background Epilepsy encompasses a group of heterogeneous brain diseases that afflict about 1% of the world’s population. Accumulating evidence shows that the immune system plays a key role in epileptogenesis. Nevertheless, the immune-related mechanisms remain not been precisely understood. Methods Three epilepsy datasets (GSE16969, GSE32534 and GSE143272) were screened to obtain differentially expressed immune-related genes (DEIRGs). Random forest (RF) and protein–protein interaction (PPI) network were constructed to identify core genes. Another dataset (GSE31718) and 60 clinical samples via quantitative real-time polymerase chain reaction (qRT-PCR) were utilized to validate core genes. Immune cell infiltration score was performed with CIBERSORTx tools and single-sample gene set enrichment analysis (ssGSEA). Gene set variation analysis (GSVA) and ssGSEA were conducted to determine the pathways that are significantly enriched during normal and epilepsy. The correlation between hub genes, immune cells, and enriched molecular pathways was evaluated by Pearson correlation analysis. Results Based on RF and PPI, 4 DEIRGs (CSF1R, IL6R, TLR2, and TNFRSF1A) were identified as hub genes. Results of qRT-PCR validated that higher expression levels of CSF1R, IL6R, TLR2, and TNFRSF1A in epilepsy samples compared to control sample. Immune infiltration analysis by CIBERSORTx displayed immune signatures that are significantly richer in epilepsy, T cell subsets in particular. Notably, ssGSEA found that Th1 signatures were more abundant in normal tissues; yet Th2 signatures were more abundant in epilepsy tissues. Cytokine cytokine receptor interaction (CCR) was significantly enriched in epilepsy based on multi-transcriptome data. Additionally, hub genes were significantly correlated with score of Th1/Th2 signatures and enrichment score of CCR in multi-transcriptome data. Conclusion Four IRGs (CSF1R, IL6R, TLR2, and TNFRSF1A) were closely correlated pathogenesis of epilepsy, which may be by impacting CCR and the balance of Th1/Th2 signatures involved in the occurrence of epilepsy. Our data offer compelling insights into the pathogenesis and promising therapeutic targets for epilepsy.

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Section: Discussionmentioning

confidence: 99%

Characterization of Immune-Related Genes and Immune Infiltration Features in Epilepsy by Multi-Transcriptome Data

Hou¹,

Chen²,

Wang³

et al. 2022

JIR

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“…Some studies have shown that purified or synthesized lipoproteins of Mycoplasma species induce inflammation through TLR2 ( Okusawa et al., 2004 ; Shimizu et al., 2005 ). And studies have confirmed that compared with the control population, TLR2 is more often highly expressed in the immune population of patients with autoimmune disease ( Marks et al., 2021 ). The lack of TLR2 expression caused by mouse germline knockout usually leads to a lack or attenuation of autoimmune inflammation ( Frasnelli et al., 2005 ; Devaraj et al., 2011 ).…”

Section: Introductionmentioning

confidence: 88%

Toll-Like Receptor 2 Modulates Pulmonary Inflammation and TNF-α Release Mediated by Mycoplasma pneumoniae

Chen

Deng

Zhao

et al. 2022

Front. Cell. Infect. Microbiol.

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ObjectivesTo investigate the roles that Toll-like receptors (TLRs) play in lung inflammation mediated by Mycoplasma pneumoniae (MP).MethodsThe changes in TLRs and tumor necrosis factor alpha (TNF-α) in peripheral blood of children with M. pneumoniae pneumonia (MPP) were monitored, and the interactions of signaling molecules regulating TNF-α release in A549 cells and neutrophils after M. pneumoniae stimulation were investigated. In TLR2 knockout (TLR2-/-) mice, the levels of TNF-α in bronchial alveolar lavage fluid (BALF) and peripheral blood after mycoplasma infection and the pathological changes in the lung tissue of mice were detected.ResultsTNF-α levels in peripheral blood of children with MPP were higher than those in non-infected children, and children with refractory MPP had the highest levels of TNF-α and TLR2. TNF-α secretion and TLR2, myeloid differentiation primary response 88 (MyD88) and phospho-p65(p-p65) levels were increased in stimulated cells. TNF-α secretion was suppressed upon siRNA-mediated TLR2 silencing. Pharmacological inhibition of nuclear factor-kappa B (NF-κB) and MyD88 effectively reduced TNF-α expression. Compared with wild-type mice, the TNF-α in serum and BALF decreased, and lung pro-inflammatory response was partially suppressed in TLR2-/- mice.ConclusionWe concluded that TLR2 regulates M. pneumoniae-mediated lung inflammation and TNF-α release through the TLR2-MyD88-NF-κB signaling pathway.

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“…Since death and severe cases of COVID-19 are associated with a hyper-inflammatory response [ 184 ], TLR2 antagonists can be tested for their capacity to alleviate the hyper-inflammatory response in SARS-CoV-2 infection or S protein stimulation. In addition, TLR2 has been demonstrated to be involved in the regulation of immune responses in autoimmune inflammatory diseases [ 185 , 186 ], kidney inflammaging [ 187 ], tissue injuries [ 71 , 188 ], gut microbiome dysbiosis [ 93 , 189 ], diabetes [ 11 ] and cancers [ 190 , 191 , 192 ].…”

Section: Therapeutic Targeting Of Tlr2 Signaling In Diseasesmentioning

confidence: 99%

The Role of TLR2 in Infectious Diseases Caused by Mycobacteria: From Cell Biology to Therapeutic Target

Spaink

2022

Biology

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Innate immunity is considered the first line of defense against microbial invasion, and its dysregulation can increase the susceptibility of hosts to infections by invading pathogens. Host cells rely on pattern recognition receptors (PRRs) to recognize invading pathogens and initiate protective innate immune responses. Toll-like receptor 2 (TLR2) is believed to be among the most important Toll-like receptors for defense against mycobacterial infection. TLR2 has been reported to have very broad functions in infectious diseases and also in other diseases, such as chronic and acute inflammatory diseases, cancers, and even metabolic disorders. However, TLR2 has an unclear dual role in both the activation and suppression of innate immune responses. Moreover, in some studies, the function of TLR2 was shown to be controversial, and therefore its role in several diseases is still inconclusive. Therefore, although TLR2 has been shown to have an important function in innate immunity, its usefulness as a therapeutic target in clinical application is still uncertain. In this literature review, we summarize the knowledge of the functions of TLR2 in host–mycobacterial interactions, discuss controversial results, and suggest possibilities for future research.

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Toll-like Receptor 2 in Autoimmune Inflammation

Cited by 34 publications

References 73 publications

Characterization of Immune-Related Genes and Immune Infiltration Features in Epilepsy by Multi-Transcriptome Data

Characterization of Immune-Related Genes and Immune Infiltration Features in Epilepsy by Multi-Transcriptome Data

Toll-Like Receptor 2 Modulates Pulmonary Inflammation and TNF-α Release Mediated by Mycoplasma pneumoniae

The Role of TLR2 in Infectious Diseases Caused by Mycobacteria: From Cell Biology to Therapeutic Target

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