Journal of Innate Immunity最新文献_第8页

Emerging Roles of cGAS-STING Signaling in Mediating Ocular Inflammation. cGAS-STING信号在介导眼部炎症中的新作用。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-10-03 DOI: 10.1159/000533897

Linbin Zhou, Bo Man Ho, Hoi Ying Emily Chan, Yan Tong, Lin Du, Jing Na He, Danny Siu-Chun Ng, Clement C Tham, Chi Pui Pang, Wai Kit Chu

{"title":"Emerging Roles of cGAS-STING Signaling in Mediating Ocular Inflammation.","authors":"Linbin Zhou, Bo Man Ho, Hoi Ying Emily Chan, Yan Tong, Lin Du, Jing Na He, Danny Siu-Chun Ng, Clement C Tham, Chi Pui Pang, Wai Kit Chu","doi":"10.1159/000533897","DOIUrl":"10.1159/000533897","url":null,"abstract":"Cyclic GMP-AMP (cGAMP) synthase (cGAS), a sensor of cytosolic DNA, recognizes cytoplasmic nucleic acids to activate the innate immune responses via generation of the second messenger cGAMP and subsequent activation of the stimulator of interferon genes (STINGs). The cGAS-STING signaling has multiple immunologic and physiological functions in all human vital organs. It mediates protective innate immune defense against DNA-containing pathogen infection, confers intrinsic antitumor immunity via detecting tumor-derived DNA, and gives rise to autoimmune and inflammatory diseases upon aberrant activation by cytosolic leakage of self-genomic and mitochondrial DNA. Disruptions in these functions are associated with the pathophysiology of various immunologic and neurodegenerative diseases. Recent evidence indicates important roles of the cGAS-STING signaling in mediating inflammatory responses in ocular inflammatory and inflammation-associated diseases, such as keratitis, diabetic retinopathy, age-related macular degeneration, and uveitis. In this review, we summarize the recently emerging evidence of cGAS-STING signaling in mediating ocular inflammatory responses and affecting pathogenesis of these complex eye diseases. We attempt to provide insightful perspectives on future directions of investigating cGAS-STING signaling in ocular inflammation. Understanding how cGAS-STING signaling is modulated to mediate ocular inflammatory responses would allow future development of novel therapeutic strategies to treat ocular inflammation and autoimmunity.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"739-750"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41135672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interactions between Macrophages and Biofilm during Staphylococcus aureus-Associated Implant Infection: Difficulties and Solutions. 金黄色葡萄球菌相关植入物感染过程中巨噬细胞与生物膜之间的相互作用：困难与解决方案。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-04-03 DOI: 10.1159/000530385

Mingzhang Li, Jinlong Yu, Geyong Guo, Hao Shen

{"title":"Interactions between Macrophages and Biofilm during Staphylococcus aureus-Associated Implant Infection: Difficulties and Solutions.","authors":"Mingzhang Li, Jinlong Yu, Geyong Guo, Hao Shen","doi":"10.1159/000530385","DOIUrl":"10.1159/000530385","url":null,"abstract":"Staphylococcus aureus (S. aureus) biofilm is the major cause of failure of implant infection treatment that results in heavy social and economic burden on individuals, families, and communities. Planktonic S. aureus attaches to medical implant surfaces where it proliferates and is wrapped by extracellular polymeric substances, forming a solid and complex biofilm. This provides a stable environment for bacterial growth, infection maintenance, and diffusion and protects the bacteria from antimicrobial agents and the immune system of the host. Macrophages are an important component of the innate immune system and resist pathogen invasion and infection through phagocytosis, antigen presentation, and cytokine secretion. The persistence, spread, or clearance of infection is determined by interplay between macrophages and S. aureus in the implant infection microenvironment. In this review, we discuss the interactions between S. aureus biofilm and macrophages, including the effects of biofilm-related bacteria on the macrophage immune response, roles of myeloid-derived suppressor cells during biofilm infection, regulation of immune cell metabolic patterns by the biofilm environment, and immune evasion strategies adopted by the biofilm against macrophages. Finally, we summarize the current methods that support macrophage-mediated removal of biofilms and emphasize the importance of considering multi-dimensions and factors related to implant-associated infection such as immunity, metabolism, the host, and the pathogen when developing new treatments.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"499-515"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10315156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9797410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Pacritinib Inhibition of IRAK1 Blocks Aberrant TLR8 Signalling by SARS-CoV-2 and HIV-1-Derived RNA. Pacritinib抑制IRAK1阻断SARS-CoV-2和hiv -1衍生RNA的异常TLR8信号传导

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2022-07-04 DOI: 10.1159/000525292

Grant R Campbell, Pratima Rawat, Stephen A Spector

引用次数: 5

Mannan-Binding Lectin Reduces Epithelial-Mesenchymal Transition in Pulmonary Fibrosis via Inactivating the Store-Operated Calcium Entry Machinery. 甘露聚糖结合凝集素通过抑制储存操作的钙进入机制减少肺纤维化的上皮-间质转化。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2022-06-07 DOI: 10.1159/000524693

Yunzhi Liu, Xianghuan Xie, Ping Wang, Jialiang Luo, Yu Chen, Qishan Xu, Jia Zhou, Xiao Lu, Jianbo Zhao, Zhengliang Chen, Daming Zuo

{"title":"Mannan-Binding Lectin Reduces Epithelial-Mesenchymal Transition in Pulmonary Fibrosis via Inactivating the Store-Operated Calcium Entry Machinery.","authors":"Yunzhi Liu, Xianghuan Xie, Ping Wang, Jialiang Luo, Yu Chen, Qishan Xu, Jia Zhou, Xiao Lu, Jianbo Zhao, Zhengliang Chen, Daming Zuo","doi":"10.1159/000524693","DOIUrl":"10.1159/000524693","url":null,"abstract":"Idiopathic pulmonary fibrosis (IPF) is a type of idiopathic interstitial pneumonia with a poor clinical prognosis. Increasing evidence has demonstrated that epithelial-mesenchymal transition (EMT) contributes to the production of pathogenic myofibroblasts and plays a pivotal role in the development of pulmonary fibrosis. Mannan-binding lectin (MBL) is a soluble calcium-dependent complement molecule. Several studies have reported associations between serum MBL levels and lung diseases; however, the effect of MBL on IPF remains unknown. The present study observed aggravated pulmonary fibrosis in bleomycin-treated MBL-/- mice compared with their wild-type counterparts. Lung tissues from bleomycin-treated MBL-/- mice displayed a more severe EMT phenotype. In vitro studies determined that MBL inhibited the EMT process through attenuating store-operated calcium entry (SOCE) signaling. It was further demonstrated that MBL promoted the ubiquitination of Orai1, an essential component of SOCE, via pyruvate dehydrogenase kinase 1 (PDK1)-serum glucocorticoid-regulated kinase 1 signaling. PDK1 inhibition abolished the MBL-mediated regulation of SOCE activity and the EMT process. Notably, biochemical analysis showed that MBL interacted with PDK1 and contributed to PDK1 ubiquitination. In summary, the present findings suggested that MBL limited the EMT phenotype in human alveolar epithelial cells through regulation of SOCE, and MBL could be recognized as a potential therapeutic target for IPF.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"1 1","pages":"37-49"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10643902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46587861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Ste20-Like Kinase TAOK1 Positively Regulates Antiviral Responses by Controlling the TBK1-IRF3 Signaling Axis. 类 Ste20 激酶 TAOK1 通过控制 TBK1-IRF3 信号轴积极调节抗病毒反应

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-01-17 DOI: 10.1159/000526324

Xiaogang Luo, Ruihua Ji, Qianru Liu, Xiaoxue Xiao, Wengang Song, Huazhang An, Yingke Li, Jun Zhou

{"title":"Ste20-Like Kinase TAOK1 Positively Regulates Antiviral Responses by Controlling the TBK1-IRF3 Signaling Axis.","authors":"Xiaogang Luo, Ruihua Ji, Qianru Liu, Xiaoxue Xiao, Wengang Song, Huazhang An, Yingke Li, Jun Zhou","doi":"10.1159/000526324","DOIUrl":"10.1159/000526324","url":null,"abstract":"The cytosolic viral nucleic acid-sensing pathways converge on the protein kinase TANK-binding kinase 1 (TBK1) and the transcription factor interferon (IFN)-regulatory factor 3 (IRF3) to induce type I IFN production and antiviral immune responses. However, the mechanism that triggers the binding of TBK1 and IRF3 after virus infection remains not fully understood. Here, we identified that thousand and one kinase 1 (TAOK1), a Ste20-like kinase, positively regulated virus-induced antiviral immune responses by controlling the TBK1-IRF3 signaling axis. Virus invasion downregulated the expression of TAOK1. TAOK1 deficiency resulted in decreased nucleic acid-mediated type I IFN production and increased susceptibility to virus infection. TAOK1 was constitutively associated with TBK1 independently of the mitochondrial antiviral signaling protein MAVS. TAOK1 promoted IRF3 activation by enhancing TBK1-IRF3 complex formation. TAOK1 enhanced virus-induced type I IFN production in a kinase activity-dependent manner. Viral infection induced TAOK1 to bind with dynein instead of microtubule-associated protein 4 (MAP4), leading to the trafficking of TBK1 to the perinuclear region to bind IRF3. Thus, the depolymerization of microtubule impaired virus-mediated IRF3 activation. Our results revealed that TAOK1 functioned as a new interaction partner and regulated antiviral signaling via trafficking TBK1 along microtubules to bind IRF3. These findings provided novel insights into the function of TAOK1 in the antiviral innate immune response and its related clinical significance.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"380-396"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/69/7e/jin-0015-0380.PMC10015707.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9116580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advanced Glycation End Products-Induced Activation of Keratinocytes: A Mechanism Underlying Cutaneous Immune Response in Psoriasis. 晚期糖基化终产物诱导角化细胞活化:银屑病皮肤免疫反应的机制。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-11-21 DOI: 10.1159/000534639

Pan Kang, Jianru Chen, Shiyu Wang, Shaolong Zhang, Shuli Li, Sen Guo, Pu Song, Ling Liu, Gang Wang, Tianwen Gao, Weigang Zhang, Chunying Li

{"title":"Advanced Glycation End Products-Induced Activation of Keratinocytes: A Mechanism Underlying Cutaneous Immune Response in Psoriasis.","authors":"Pan Kang, Jianru Chen, Shiyu Wang, Shaolong Zhang, Shuli Li, Sen Guo, Pu Song, Ling Liu, Gang Wang, Tianwen Gao, Weigang Zhang, Chunying Li","doi":"10.1159/000534639","DOIUrl":"10.1159/000534639","url":null,"abstract":"Psoriasis is a common inflammatory skin disease, in which epidermal keratinocytes play a vital role in its pathogenesis by acting both as the responder and as the accelerator to the cutaneous psoriatic immune response. Advanced glycation end products (AGEs) are a class of proinflammatory metabolites that are commonly accumulating in cardiometabolic disorders. Recent studies have also observed the increased level of AGEs in the serum and skin of psoriasis patients, but the role of AGEs in psoriatic inflammation has not been well investigated. In the present study, we initially detected abnormal accumulation of AGEs in epidermal keratinocytes of psoriatic lesions collected from psoriasis patients. Furthermore, AGEs promoted the proliferation of keratinocytes via upregulated Keratin 17 (K17)-mediated p27KIP1 inhibition followed by accelerated cell cycle progression. More importantly, AGEs facilitated the production of interleukin-36 alpha (IL-36α) in keratinocytes, which could enhance T helper 17 (Th17) immune response. In addition, the induction of both K17 and IL-36α by AGEs in keratinocytes was dependent on the activation of signal transducer and activator of transcription 1/3 (STAT1/3) signaling pathways. At last, the effects of AGEs on keratinocytes were mediated by the receptor for AGEs (RAGE). Taken together, these findings support that AGEs potentiate the innate immune function of keratinocytes, which contributes to the formation of psoriatic inflammation. Our study implicates AGEs as a potential pathogenic link between psoriasis and cardiometabolic comorbidities.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"876-892"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10715758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138291090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human Monocytes Exposed to SARS-CoV-2 Display Features of Innate Immune Memory Producing High Levels of CXCL10 upon Restimulation. 暴露于SARS-CoV-2的人单核细胞表现出先天免疫记忆的特征，在再刺激时产生高水平的CXCL10。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-11-21 DOI: 10.1159/000535120

Jelena Cvetkovic, Ronald H J Jacobi, Alberto Miranda-Bedate, Nhung Pham, Martina Kutmon, James Groot, Martijn D B van de Garde, Elena Pinelli

{"title":"Human Monocytes Exposed to SARS-CoV-2 Display Features of Innate Immune Memory Producing High Levels of CXCL10 upon Restimulation.","authors":"Jelena Cvetkovic, Ronald H J Jacobi, Alberto Miranda-Bedate, Nhung Pham, Martina Kutmon, James Groot, Martijn D B van de Garde, Elena Pinelli","doi":"10.1159/000535120","DOIUrl":"10.1159/000535120","url":null,"abstract":"Introduction: A role for innate immune memory in protection during COVID-19 infection or vaccination has been recently reported. However, no study so far has shown whether the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can train innate immune cells. The aim of this study was to investigate whether this virus can induce trained immunity in human monocytes.Methods: Monocytes were exposed to inactivated SARS-CoV-2 (iSARS-CoV-2) for 24 h, followed by a resting period in the medium only and a secondary stimulation on day 6 after which the cytokine/chemokine and transcriptomic profiles were determined.Results: Compared to untrained cells, the iSARS-CoV-2-trained monocytes secreted significantly higher levels of IL-6, TNF-α, CXCL10, CXCL9, and CXCL11 upon restimulation. Transcriptome analysis of iSARS-CoV-2-trained monocytes revealed increased expression of several inflammatory genes. As epigenetic and metabolic modifications are hallmarks of trained immunity, we analyzed the expression of genes related to these processes. Findings indicate that indeed SARS-CoV-2-trained monocytes show changes in the expression of genes involved in metabolic pathways including the tricarboxylic acid cycle, amino acid metabolism, and the expression of several epigenetic regulator genes. Using epigenetic inhibitors that block histone methyl and acetyltransferases, we observed that the capacity of monocytes to be trained by iSARS-CoV-2 was abolished.Conclusion: Overall, our findings indicate that iSARS-CoV-2 can induce properties associated with trained immunity in human monocytes. These results contribute to the knowledge required for improving vaccination strategies to prevent infectious diseases.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"911-924"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10718582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138291091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of Changes in Human Airway Epithelial Cellular Composition and Differentiation on SARS-CoV-2 Infection Biology. 人类气道上皮细胞组成和分化的变化对 SARS-CoV-2 感染生物学的影响

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-03-25 DOI: 10.1159/000530374

Melissa Thaler, Ying Wang, Anne M van der Does, Alen Faiz, Dennis K Ninaber, Natacha S Ogando, Hendrik Beckert, Christian Taube, Clarisse Salgado-Benvindo, Eric J Snijder, Peter J Bredenbeek, Pieter S Hiemstra, Martijn J van Hemert

{"title":"Impact of Changes in Human Airway Epithelial Cellular Composition and Differentiation on SARS-CoV-2 Infection Biology.","authors":"Melissa Thaler, Ying Wang, Anne M van der Does, Alen Faiz, Dennis K Ninaber, Natacha S Ogando, Hendrik Beckert, Christian Taube, Clarisse Salgado-Benvindo, Eric J Snijder, Peter J Bredenbeek, Pieter S Hiemstra, Martijn J van Hemert","doi":"10.1159/000530374","DOIUrl":"10.1159/000530374","url":null,"abstract":"The consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can range from asymptomatic to fatal disease. Variations in epithelial susceptibility to SARS-CoV-2 infection depend on the anatomical location from the proximal to distal respiratory tract. However, the cellular biology underlying these variations is not completely understood. Thus, air-liquid interface cultures of well-differentiated primary human tracheal and bronchial epithelial cells were employed to study the impact of epithelial cellular composition and differentiation on SARS-CoV-2 infection by transcriptional (RNA sequencing) and immunofluorescent analyses. Changes of cellular composition were investigated by varying time of differentiation or by using specific compounds. We found that SARS-CoV-2 primarily infected not only ciliated cells but also goblet cells and transient secretory cells. Viral replication was impacted by differences in cellular composition, which depended on culturing time and anatomical origin. A higher percentage of ciliated cells correlated with a higher viral load. However, DAPT treatment, which increased the number of ciliated cells and reduced goblet cells, decreased viral load, indicating the contribution of goblet cells to infection. Cell entry factors, especially cathepsin L and transmembrane protease serine 2, were also affected by differentiation time. In conclusion, our study demonstrates that viral replication is affected by changes in cellular composition, especially in cells related to the mucociliary system. This could explain in part the variable susceptibility to SARS-CoV-2 infection between individuals and between anatomical locations in the respiratory tract.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"562-580"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/48/f5/jin-2023-0015-0001-530374.PMC10315690.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9774994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondrial Damage-Associated Molecular Patterns and Metabolism in the Regulation of Innate Immunity. 线粒体损伤相关分子模式和代谢在先天免疫调节中的作用。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-09-04 DOI: 10.1159/000533602

Yanmin Lyu, Tianyu Wang, Shuhong Huang, Zhaoqiang Zhang

{"title":"Mitochondrial Damage-Associated Molecular Patterns and Metabolism in the Regulation of Innate Immunity.","authors":"Yanmin Lyu, Tianyu Wang, Shuhong Huang, Zhaoqiang Zhang","doi":"10.1159/000533602","DOIUrl":"10.1159/000533602","url":null,"abstract":"The innate immune system, as the host's first line of defense against intruders, plays a critical role in recognizing, identifying, and reacting to a wide range of microbial intruders. There is increasing evidence that mitochondrial stress is a major initiator of innate immune responses. When mitochondria's integrity is disrupted or dysfunction occurs, the mitochondria's contents are released into the cytosol. These contents, like reactive oxygen species, mitochondrial DNA, and double-stranded RNA, among others, act as damage-related molecular patterns (DAMPs) that can bind to multiple innate immune sensors, particularly pattern recognition receptors, thereby leading to inflammation. To avoid the production of DAMPs, in addition to safeguarding organelles integrity and functionality, mitochondria may activate mitophagy or apoptosis. Moreover, mitochondrial components and specific metabolic regulations modify properties of innate immune cells. These include macrophages, dendritic cells, innate lymphoid cells, and so on, in steady state or in stimulation that are involved in processes ranging from the tricarboxylic acid cycle to oxidative phosphorylation and fatty acid metabolism. Here we provide a brief summary of mitochondrial DAMPs' initiated and potentiated inflammatory response in the innate immune system. We also provide insights into how the state of activation, differentiation, and functional polarization of innate immune cells can be influenced by alteration to the metabolic pathways in mitochondria.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"665-679"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/23/e7/jin-2023-0015-0001-533602.PMC10601681.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10156317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TLR7 Activation in M-CSF-Dependent Monocyte-Derived Human Macrophages Potentiates Inflammatory Responses and Prompts Neutrophil Recruitment. M-CSF 依赖性单核细胞衍生的人类巨噬细胞中的 TLR7 激活可增强炎症反应并促进中性粒细胞的招募。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-04-11 DOI: 10.1159/000530249

Miriam Simón-Fuentes, Cristina Herrero, Lucia Acero-Riaguas, Concha Nieto, Fatima Lasala, Nuria Labiod, Joanna Luczkowiak, Bárbara Alonso, Rafael Delgado, Maria Colmenares, Ángel L Corbí, Ángeles Domínguez-Soto

{"title":"TLR7 Activation in M-CSF-Dependent Monocyte-Derived Human Macrophages Potentiates Inflammatory Responses and Prompts Neutrophil Recruitment.","authors":"Miriam Simón-Fuentes, Cristina Herrero, Lucia Acero-Riaguas, Concha Nieto, Fatima Lasala, Nuria Labiod, Joanna Luczkowiak, Bárbara Alonso, Rafael Delgado, Maria Colmenares, Ángel L Corbí, Ángeles Domínguez-Soto","doi":"10.1159/000530249","DOIUrl":"10.1159/000530249","url":null,"abstract":"Toll-like receptor 7 (TLR7) is an endosomal pathogen-associated molecular pattern (PAMP) receptor that senses single-stranded RNA (ssRNA) and whose engagement results in the production of type I IFN and pro-inflammatory cytokines upon viral exposure. Recent genetic studies have established that a dysfunctional TLR7-initiated signaling is directly linked to the development of inflammatory responses. We present evidence that TLR7 is preferentially expressed by monocyte-derived macrophages generated in the presence of M-CSF (M-MØ). We now show that TLR7 activation in M-MØ triggers a weak MAPK, NFκB, and STAT1 activation and results in low production of type I IFN. Of note, TLR7 engagement reprograms MAFB+ M-MØ towards a pro-inflammatory transcriptional profile characterized by the expression of neutrophil-attracting chemokines (CXCL1-3, CXCL5, CXCL8), whose expression is dependent on the transcription factors MAFB and AhR. Moreover, TLR7-activated M-MØ display enhanced pro-inflammatory responses and a stronger production of neutrophil-attracting chemokines upon secondary stimulation. As aberrant TLR7 signaling and enhanced pulmonary neutrophil/lymphocyte ratio associate with impaired resolution of virus-induced inflammatory responses, these results suggest that targeting macrophage TLR7 might be a therapeutic strategy for viral infections where monocyte-derived macrophages exhibit a pathogenic role.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"517-530"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10315069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9744985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0