Journal of Innate Immunity最新文献_第10页

The Citrullination-Neutrophil Extracellular Trap Axis in Chronic Diseases 慢性疾病中的瓜氨酸-中性粒细胞胞外陷阱轴

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2022-03-09 DOI: 10.1159/000522331

M. Marônek, R. Gardlík

{"title":"The Citrullination-Neutrophil Extracellular Trap Axis in Chronic Diseases","authors":"M. Marônek, R. Gardlík","doi":"10.1159/000522331","DOIUrl":"https://doi.org/10.1159/000522331","url":null,"abstract":"Citrullination of proteins is crucial for the formation of neutrophil extracellular traps (NETs) – strands of nuclear DNA expulsed in the extracellular environment along with antimicrobial proteins in order to halt the spread of pathogens. Paradoxically, NETs may be immunogenic and contribute to inflammation. It is known that for the externalization of DNA, a group of enzymes called peptidyl arginine deiminases (PADs) is required. Current research often looks at citrullination, NET formation, PAD overexpression, and extracellular DNA (ecDNA) accumulation in chronic diseases as separate events. In contrast, we propose that citrullination can be viewed as the primary mechanism of autoimmunity, for instance by the formation of anti-citrullinated protein antibodies (ACPAs) but also as a process contributing to chronic inflammation. Therefore, citrullination could be at the center, connecting and impacting multiple inflammatory diseases in which ACPAs, NETs, or ecDNA have already been documented. In this review, we aimed to highlight the importance of citrullination in the etiopathogenesis of a number of chronic diseases and to explore the diagnostic, prognostic, and therapeutic potential of the citrullination-NET axis.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"14 1","pages":"393 - 417"},"PeriodicalIF":5.3,"publicationDate":"2022-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45194417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Streptococcus pneumoniae Impairs Maturation of Human Dendritic Cells and Consequent Activation of CD4+ T Cells via Pneumolysin 肺炎链球菌通过溶血素阻碍人树突状细胞的成熟和CD4+T细胞的活化

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2022-03-04 DOI: 10.1159/000522339

Antje D. Paulikat, Lea A. Tölken, Lana H. Jachmann, G. Burchhardt, S. Hammerschmidt, N. Siemens

{"title":"Streptococcus pneumoniae Impairs Maturation of Human Dendritic Cells and Consequent Activation of CD4+ T Cells via Pneumolysin","authors":"Antje D. Paulikat, Lea A. Tölken, Lana H. Jachmann, G. Burchhardt, S. Hammerschmidt, N. Siemens","doi":"10.1159/000522339","DOIUrl":"https://doi.org/10.1159/000522339","url":null,"abstract":"Influenza A Virus (IAV), Staphylococcus aureus (staphylococci), and Streptococcus pneumoniae (pneumococci) are leading viral and bacterial causes of pneumonia. Dendritic cells (DCs) are present in the lower respiratory tract. They are characterized by low expression of co-stimulatory molecules, including CD80 and CD86 and high capacity of antigen uptake. Subsequently, DCs upregulate co-stimulatory signals and cytokine secretion to effectively induce T-cell priming. Here, we investigated these processes in response to bacterial and viral single as well as coinfections using human monocyte-derived (mo)DCs. Irrespective of single or coinfections, moDCs matured in response to IAV and/or staphylococcal infections, secreted a wide range of cytokines, and activated CD4+, CD8+ as well as double-negative T cells. In contrast, pneumococcal single and coinfections impaired moDC maturation, which was characterized by low expression of CD80 and CD86, downregulated expression of CD40, and a mild cytokine release resulting in abrogated CD4+ T-cell activation. These actions were attributed to the cholesterol-dependent cytotoxin pneumolysin (Ply). Infections with a ply-deficient mutant resulted in restored moDC maturation and exclusive CD4+ T-cell activation. These findings show that Ply has important immunomodulatory functions, supporting further investigations in specific modalities of Ply-DC interplay.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"14 1","pages":"569 - 580"},"PeriodicalIF":5.3,"publicationDate":"2022-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46445332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Calcineurin Aα Contributes to IgE-Dependent Mast-Cell Mediator Secretion in Allergic Inflammation. 钙调磷酸酶Aα参与过敏性炎症中ige依赖性肥大细胞介质的分泌。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2022-01-01 Epub Date: 2021-11-26 DOI: 10.1159/000520040

Edwin Leong, Zheng Pang, Andrew W Stadnyk, Tong-Jun Lin

{"title":"Calcineurin Aα Contributes to IgE-Dependent Mast-Cell Mediator Secretion in Allergic Inflammation.","authors":"Edwin Leong, Zheng Pang, Andrew W Stadnyk, Tong-Jun Lin","doi":"10.1159/000520040","DOIUrl":"https://doi.org/10.1159/000520040","url":null,"abstract":"Mast cells (MCs) are key mediators of allergic inflammation through the activation of cross-linked immunoglobulin E (IgE) bound to the high-affinity IgE receptor (FcϵRI) on the cell surface, leading to the release of biologically potent mediators, either from preformed granules or newly synthesized. Pharmacological inhibitors have been developed to target a key signaling protein phosphatase in this pathway, calcineurin, yet there is a lack of genetic and definitive evidence for the various isoforms of calcineurin subunits in FcϵRI-mediated responses. In this study, we hypothesized that deficiency in the calcineurin Aα isoform will result in a decreased allergic immune response by the MCs. In a model of passive cutaneous anaphylaxis, there was a reduction in vascular permeability in MC-deficient mouse tissues reconstituted with calcineurin subunit A (CnAα) gene-knockout (CnAα-/-) MCs, and in vitro experiments identified a significant reduction in release of preformed mediators from granules. Furthermore, released levels of de novo synthesized cytokines were reduced upon FcϵRI activation of CnAα-/- MCs in vitro. Characterizing the mechanisms associated with this deficit response, we found a significant impairment of nuclear factor of kappa light polypeptide gene enhancer in B cell phosphorylation and impaired nuclear factor kappa-light-chain-enhancer of activated B-cell inhibitor alpha (NF-κB) activation. Thus, we concluded that CnAα contributes to the release of preformed mediators and newly synthesized mediators from FcϵRI-mediated activation of MCs, and this regulation includes NF-κB signaling.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"14 4","pages":"320-334"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9c/43/jin-0014-0320.PMC9274814.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39785403","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

Macrophage-Biomimetic Nanoparticles Ameliorate Ulcerative Colitis through Reducing Inflammatory Factors Expression. 巨噬细胞仿生纳米颗粒通过降低炎症因子表达改善溃疡性结肠炎。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2022-01-01 Epub Date: 2021-11-01 DOI: 10.1159/000519363

Zhengshuo Li, Xiaoyue Zhang, Can Liu, Qiu Peng, Yangge Wu, Yuqing Wen, Run Zheng, Qun Yan, Jian Ma

{"title":"Macrophage-Biomimetic Nanoparticles Ameliorate Ulcerative Colitis through Reducing Inflammatory Factors Expression.","authors":"Zhengshuo Li, Xiaoyue Zhang, Can Liu, Qiu Peng, Yangge Wu, Yuqing Wen, Run Zheng, Qun Yan, Jian Ma","doi":"10.1159/000519363","DOIUrl":"https://doi.org/10.1159/000519363","url":null,"abstract":"Background and aims: Inflammatory mediator S100A9 is dramatically elevated in ulcerative colitis and correlates with disease severity. S100A9 is a potential molecule to target for the treatment of colitis, but to date, there is no effective targeting method. The aim of this study was to develop a safe and effective nano-delivery system targeting S100A9 and to evaluate its therapeutic efficacy in ulcerative colitis mouse model.Methods: We designed an oral nano-delivery system using poly (lactic acid-glycolic acid) (PLGA)-loaded S100A9 inhibitor tasquinimod to synthesize PLGA-TAS nanoparticles. TLR4-overexpressing macrophage membranes (MMs) were used to wrap the nanoparticles to make MM-PLGA-TAS, which allowed the nanoparticles to acquire the ability to specifically enrich the colitis region.Results: MM-PLGA-TAS was endocytosed by inflammatory phenotype RAW264.7 cells in vitro and can efficiently enrich in inflamed mouse colitis tissue in vivo. A chemically induced ulcerative colitis mouse model was used to evaluate the therapeutic effect of oral MM-PLGA-TAS. MM-PLGA-TAS significantly alleviated the symptoms of ulcerative colitis, and mechanically, MM-PLGA-TAS achieved immunomodulatory and suppressive effects by reducing S100a9 and other cytokines in the colitis region.Conclusion: We describe a convenient, orally targeted colitis drug delivery system that cures the disease in ulcerative colitis mice. This system substantially increases drug accumulation in inflamed colonic tissue, reduces the risk of systemic exposure, and is a promising therapeutic approach against ulcerative colitis.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"14 4","pages":"380-392"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/93/26/jin-0014-0380.PMC9274947.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39834780","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: 12

Innate Immune Training with Bacterial Extracts Enhances Lung Macrophage Recruitment to Protect from Betacoronavirus Infection. 用细菌提取物进行先天免疫训练可增强肺巨噬细胞募集以保护免受冠状病毒感染。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2022-01-01 Epub Date: 2021-11-12 DOI: 10.1159/000519699

Manuel Salzmann, Patrick Haider, Christoph Kaun, Mira Brekalo, Boris Hartmann, Theresia Lengheimer, Rebecca Pichler, Thomas Filip, Sophia Derdak, Bruno Podesser, Christian Hengstenberg, Walter S Speidl, Johann Wojta, Roberto Plasenzotti, Philipp J Hohensinner

{"title":"Innate Immune Training with Bacterial Extracts Enhances Lung Macrophage Recruitment to Protect from Betacoronavirus Infection.","authors":"Manuel Salzmann, Patrick Haider, Christoph Kaun, Mira Brekalo, Boris Hartmann, Theresia Lengheimer, Rebecca Pichler, Thomas Filip, Sophia Derdak, Bruno Podesser, Christian Hengstenberg, Walter S Speidl, Johann Wojta, Roberto Plasenzotti, Philipp J Hohensinner","doi":"10.1159/000519699","DOIUrl":"https://doi.org/10.1159/000519699","url":null,"abstract":"Training of the innate immune system with orally ingested bacterial extracts was demonstrated to have beneficial effects on infection clearance and disease outcome. The aim of our study was to identify cellular and molecular processes responsible for these immunological benefits. We used a murine coronavirus (MCoV) A59 mouse model treated with the immune activating bacterial extract Broncho-Vaxom (BV) OM-85. Tissue samples were analysed with qPCR, RNA sequencing, histology, and flow cytometry. After BV OM-85 treatment, interstitial macrophages accumulated in lung tissue leading to a faster response of type I interferon (IFN) signalling after MCoV infection resulting in overall lung tissue protection. Moreover, RNA sequencing showed that lung tissue from mice receiving BV OM-85 resembled an intermediate stage between healthy and viral infected lung tissue at day 4, indicating a faster return to normal tissue homoeostasis. The pharmacologic effect was mimicked by adoptively transferring naive lung macrophages into lungs from recipient mice before virus infection. The beneficial effect of BV OM-85 was abolished when inhibiting initial type I IFN signalling. Overall, our data suggest that BV OM-85 enhances lung macrophages allowing for a faster IFN response towards a viral challenge as part of the oral-induced innate immune system training.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"14 4","pages":"293-305"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a2/9e/jin-0014-0293.PMC9059017.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39710199","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: 13

Staphylococcus aureus Activates the Aryl Hydrocarbon Receptor in Human Keratinocytes. 金黄色葡萄球菌激活人角质形成细胞中的芳烃受体。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2022-01-01 DOI: 10.1159/000524033

Eva-Lena Stange, Franziska Rademacher, Katharina Antonia Drerup, Nina Heinemann, Lena Möbus, Regine Gläser, Jürgen Harder

{"title":"Staphylococcus aureus Activates the Aryl Hydrocarbon Receptor in Human Keratinocytes.","authors":"Eva-Lena Stange, Franziska Rademacher, Katharina Antonia Drerup, Nina Heinemann, Lena Möbus, Regine Gläser, Jürgen Harder","doi":"10.1159/000524033","DOIUrl":"https://doi.org/10.1159/000524033","url":null,"abstract":"Staphylococcus aureus is an important pathogen causing various infections, including - as most frequently isolated bacterium - cutaneous infections. Keratinocytes as the first barrier cells of the skin respond to S. aureus by the release of defense molecules such as cytokines and antimicrobial peptides. Although several pattern recognition receptors expressed in keratinocytes such as Toll-like and NOD-like receptors have been reported to detect the presence of S. aureus, the mechanisms underlying the interplay between S. aureus and keratinocytes are still emerging. Here, we report that S. aureus induced gene expression of CYP1A1 and CYP1B1, responsive genes of the aryl hydrocarbon receptor (AhR). AhR activation by S. aureus was further confirmed by AhR gene reporter assays. AhR activation was mediated by factor(s) <2 kDa secreted by S. aureus. Whole transcriptome analyses and real-time PCR analyses identified IL-24, IL-6, and IL-1beta as cytokines induced in an AhR-dependent manner in S. aureus-treated keratinocytes. AhR inhibition in a 3D organotypic skin equivalent confirmed the crucial role of the AhR in mediating the induction of IL-24, IL-6, and IL-1beta upon stimulation with living S. aureus. Taken together, we further highlight the important role of the AhR in cutaneous innate defense and identified the AhR as a novel receptor mediating the sensing of the important skin pathogen S. aureus in keratinocytes.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"14 6","pages":"582-592"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0a/e8/jin-0014-0582.PMC9801257.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10459819","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

Lipidomic Profiling of Bronchoalveolar Lavage Fluid Extracellular Vesicles Indicates Their Involvement in Lipopolysaccharide-Induced Acute Lung Injury. 支气管肺泡灌洗液细胞外囊泡的脂质组学分析表明它们参与了脂多糖诱发的急性肺损伤。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2022-01-01 Epub Date: 2022-04-01 DOI: 10.1159/000522338

Teja Srinivas Nirujogi, Sainath R Kotha, Sangwoon Chung, Brenda F Reader, Anita Yenigalla, Liwen Zhang, John P Shapiro, Jon Wisler, John W Christman, Krishnarao Maddipati, Narasimham L Parinandi, Manjula Karpurapu

{"title":"Lipidomic Profiling of Bronchoalveolar Lavage Fluid Extracellular Vesicles Indicates Their Involvement in Lipopolysaccharide-Induced Acute Lung Injury.","authors":"Teja Srinivas Nirujogi, Sainath R Kotha, Sangwoon Chung, Brenda F Reader, Anita Yenigalla, Liwen Zhang, John P Shapiro, Jon Wisler, John W Christman, Krishnarao Maddipati, Narasimham L Parinandi, Manjula Karpurapu","doi":"10.1159/000522338","DOIUrl":"10.1159/000522338","url":null,"abstract":"Emerging data support the pivotal role of extracellular vesicles (EVs) in normal cellular physiology and disease conditions. However, despite their abundance, there is much less information about the lipid mediators carried in EVs, especially in the context of acute lung injury (ALI). Our data demonstrate that C57BL/6 mice subjected to intranasal Escherichia coli lipopolysaccharide (LPS)-induced ALI release, a higher number of EVs into the alveolar space, compared to saline-treated controls. EVs released during ALI originated from alveolar epithelial cells, macrophages, and neutrophils and carry a diverse array of lipid mediators derived from ω-3 and ω-6 polyunsaturated fatty acids (PUFA). The eicosanoids in EVs correlated with cellular levels of arachidonic acid, expression of cytosolic phospholipase A2, cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome epoxygenase p450 proteins in pulmonary macrophages. Furthermore, EVs from LPS-toll-like receptor 4 knockout (TLR4-/-) mice contained significantly lower amounts of COX and LOX catalyzed eicosanoids and ω-3 PUFA metabolites. More importantly, EVs from LPS-treated wild-type mice increased TNF-α release by macrophages and reduced alveolar epithelial monolayer barrier integrity compared to EVs from LPS-treated TLR4-/- mice. In summary, our study demonstrates for the first time that the EV carried PUFA metabolite profile in part depends on the inflammatory status of the lung macrophages and modulates pulmonary macrophage and alveolar epithelial cell function during LPS-induced ALI.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"14 5","pages":"555-568"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/56/7d/jin-0014-0555.PMC9485986.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9320683","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

Hydrogen Peroxide Is Crucial for NLRP3 Inflammasome-Mediated IL-1β Production and Cell Death in Pneumococcal Infections of Bronchial Epithelial Cells. 过氧化氢对肺炎球菌感染支气管上皮细胞NLRP3炎症小体介导的IL-1β产生和细胞死亡至关重要

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2022-01-01 DOI: 10.1159/000517855

Surabhi Surabhi, Lana H Jachmann, Patience Shumba, Gerhard Burchhardt, Sven Hammerschmidt, Nikolai Siemens

{"title":"Hydrogen Peroxide Is Crucial for NLRP3 Inflammasome-Mediated IL-1β Production and Cell Death in Pneumococcal Infections of Bronchial Epithelial Cells.","authors":"Surabhi Surabhi, Lana H Jachmann, Patience Shumba, Gerhard Burchhardt, Sven Hammerschmidt, Nikolai Siemens","doi":"10.1159/000517855","DOIUrl":"https://doi.org/10.1159/000517855","url":null,"abstract":"Epithelial cells play a crucial role in detection of the pathogens as well as in initiation of the host immune response. Streptococcus pneumoniae (pneumococcus) is a typical colonizer of the human nasopharynx, which can disseminate to the lower respiratory tract and subsequently cause severe invasive diseases such as pneumonia, sepsis, and meningitis. Hydrogen peroxide (H2O2) is produced by pneumococci as a product of the pyruvate oxidase SpxB. However, its role as a virulence determinant in pneumococcal infections of the lower respiratory tract is not well understood. In this study, we investigated the role of pneumococcal-derived H2O2 in initiating epithelial cell death by analyzing the interplay between 2 key cell death pathways, namely, apoptosis and pyroptosis. We demonstrate that H2O2 primes as well as activates the NLRP3 inflammasome and thereby mediates IL-1β production and release. Furthermore, we show that pneumococcal H2O2 causes cell death via the activation of both apoptotic as well as pyroptotic pathways which are mediated by the activation of caspase-3/7 and caspase-1, respectively. However, H2O2-mediated IL-1β release itself occurs mainly via apoptosis.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"14 3","pages":"192-206"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9149442/pdf/jin-0014-0192.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9231153","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: 19

HMGB1-Like Dorsal Switch Protein 1 Triggers a Damage Signal in Mosquito Gut to Activate Dual Oxidase via Eicosanoids. hmgb1样背侧开关蛋白1触发蚊子肠道损伤信号，通过类二十烷激活双氧化酶

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2022-01-01 DOI: 10.1159/000524561

Shabbir Ahmed, Seyedeh Minoo Sajjadian, Yonggyun Kim

{"title":"HMGB1-Like Dorsal Switch Protein 1 Triggers a Damage Signal in Mosquito Gut to Activate Dual Oxidase via Eicosanoids.","authors":"Shabbir Ahmed, Seyedeh Minoo Sajjadian, Yonggyun Kim","doi":"10.1159/000524561","DOIUrl":"https://doi.org/10.1159/000524561","url":null,"abstract":"Several mosquitoes transmit human pathogens by blood feeding, with the gut being the main entrance for the pathogens. Thus, the gut epithelium defends the pathogens by eliciting potent immune responses. However, it was unclear how the mosquito gut discriminates pathogens among various microflora in the lumen. This study proposed a hypothesis that a damage signal might be specifically induced by pathogens in the gut. The Asian tiger mosquito, Aedes albopictus, encodes dorsal switch protein 1 (Aa-DSP1) as a putative damage-associated molecular pattern (DAMP). Aa-DSP1 was localized in the nucleus of the midgut epithelium in naïve larvae. Upon infection by a pathogenic bacterium, Serratia marcescens, Aa-DSP1 was released to hemocoel and activated phospholipase A2 (PLA2). The activated PLA2 increased the level of prostaglandin E2 (PGE2) in the gut and subsequently increased Ca2+ signal to produce reactive oxygen species (ROS) via dual oxidase (Duox). Inhibition of Aa-DSP1 via RNA interference or specific inhibitor treatment failed to increase PGE2/Ca2+ signal upon the bacterial infection. Thus, the inhibitors specifically targeting eicosanoid biosynthesis significantly prevented the upregulation of ROS production in the gut and enhanced mosquito mortality after the bacterial infection. However, such inhibitory effects were rescued by adding PGE2. These suggest that Aa-DSP1 plays an important role in immune response of the mosquito gut as a DAMP during pathogen infection by triggering a signaling pathway, DSP1/PLA2/Ca2+/Duox.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"14 6","pages":"657-672"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fb/28/jin-0014-0657.PMC9801255.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9638108","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: 8

Yin and Yang of Biofilm Formation and Cyclic di-GMP Signaling of the Gastrointestinal Pathogen Salmonella enterica Serovar Typhimurium. 胃肠道致病菌肠炎沙门氏菌血清型鼠伤寒沙门氏菌生物膜形成的阴阳与循环二gmp信号传导。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2022-01-01 Epub Date: 2021-11-12 DOI: 10.1159/000519573

Agaristi Lamprokostopoulou, Ute Römling

{"title":"Yin and Yang of Biofilm Formation and Cyclic di-GMP Signaling of the Gastrointestinal Pathogen Salmonella enterica Serovar Typhimurium.","authors":"Agaristi Lamprokostopoulou, Ute Römling","doi":"10.1159/000519573","DOIUrl":"https://doi.org/10.1159/000519573","url":null,"abstract":"Within the last 60 years, microbiological research has challenged many dogmas such as bacteria being unicellular microorganisms directed by nutrient sources; these investigations produced new dogmas such as cyclic diguanylate monophosphate (cyclic di-GMP) second messenger signaling as a ubiquitous regulator of the fundamental sessility/motility lifestyle switch on the single-cell level. Successive investigations have not yet challenged this view; however, the complexity of cyclic di-GMP as an intracellular bacterial signal, and, less explored, as an extracellular signaling molecule in combination with the conformational flexibility of the molecule, provides endless opportunities for cross-kingdom interactions. Cyclic di-GMP-directed microbial biofilms commonly stimulate the immune system on a lower level, whereas host-sensed cyclic di-GMP broadly stimulates the innate and adaptive immune responses. Furthermore, while the intracellular second messenger cyclic di-GMP signaling promotes bacterial biofilm formation and chronic infections, oppositely, Salmonella Typhimurium cellulose biofilm inside immune cells is not endorsed. These observations only touch on the complexity of the interaction of biofilm microbial cells with its host. In this review, we describe the Yin and Yang interactive concepts of biofilm formation and cyclic di-GMP signaling using S. Typhimurium as an example.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"14 4","pages":"275-292"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39710196","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: 8