Journal of Innate Immunity最新文献_第9页

Mesenchymal Stromal Cells Facilitate Neutrophil-Trained Immunity by Reprogramming Hematopoietic Stem Cells. 间充质基质细胞通过重新编程造血干细胞促进中性粒细胞训练的免疫。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-10-05 DOI: 10.1159/000533732

Julie Ng, Anna E Marneth, Alec Griffith, Daniel Younger, Sailaja Ghanta, Alan Jiao, Gareth Willis, Junwen Han, Jewel Imani, Bailin Niu, Joshua W Keegan, Brandon Hancock, Fei Guo, Yang Shi, Mark A Perrella, James A Lederer

{"title":"Mesenchymal Stromal Cells Facilitate Neutrophil-Trained Immunity by Reprogramming Hematopoietic Stem Cells.","authors":"Julie Ng, Anna E Marneth, Alec Griffith, Daniel Younger, Sailaja Ghanta, Alan Jiao, Gareth Willis, Junwen Han, Jewel Imani, Bailin Niu, Joshua W Keegan, Brandon Hancock, Fei Guo, Yang Shi, Mark A Perrella, James A Lederer","doi":"10.1159/000533732","DOIUrl":"10.1159/000533732","url":null,"abstract":"Novel therapeutics are urgently needed to prevent opportunistic infections in immunocompromised individuals undergoing cancer treatments or other immune-suppressive therapies. Trained immunity is a promising strategy to reduce this burden of disease. We previously demonstrated that mesenchymal stromal cells (MSCs) preconditioned with a class A CpG oligodeoxynucleotide (CpG-ODN), a Toll-like receptor 9 (TLR9) agonist, can augment emergency granulopoiesis in a murine model of neutropenic sepsis. Here, we used a chimeric mouse model to demonstrate that MSCs secrete paracrine factors that act on lineage-negative c-kit+ hematopoietic stem cells (HSCs), leaving them \"poised\" to enhance emergency granulopoiesis months after transplantation. Chimeric mice developed from HSCs exposed to conditioned media from MSCs and CpG-ODN-preconditioned MSCs showed significantly higher bacterial clearance and increased neutrophil granulopoiesis following lung infection than control mice. By Cleavage Under Targets and Release Using Nuclease (CUT&RUN) chromatin sequencing, we identified that MSC-conditioned media leaves H3K4me3 histone marks in HSCs at genes involved in myelopoiesis and in signaling persistence by the mTOR pathway. Both soluble factors and extracellular vesicles from MSCs mediated these effects on HSCs and proteomic analysis by mass spectrometry revealed soluble calreticulin as a potential mediator. In summary, this study demonstrates that trained immunity can be mediated by paracrine factors from MSCs to induce neutrophil-trained immunity by reprogramming HSCs for long-lasting functional changes in neutrophil-mediated antimicrobial immunity.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"765-781"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10622164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41140472","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

Tollip Inhibits IL-33 Release and Inflammation in Influenza A Virus-Infected Mouse Airways. Tollip抑制甲型流感病毒感染小鼠气道IL-33释放和炎症。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2022-06-27 DOI: 10.1159/000525315

Niccolette Schaunaman, Kris Genelyn Dimasuay, Diana Cervantes, Liwu Li, Mari Numata, Monica Kraft, Hong Wei Chu

{"title":"Tollip Inhibits IL-33 Release and Inflammation in Influenza A Virus-Infected Mouse Airways.","authors":"Niccolette Schaunaman, Kris Genelyn Dimasuay, Diana Cervantes, Liwu Li, Mari Numata, Monica Kraft, Hong Wei Chu","doi":"10.1159/000525315","DOIUrl":"10.1159/000525315","url":null,"abstract":"Respiratory influenza A virus (IAV) infection continues to pose significant challenges in healthcare of human diseases including asthma. IAV infection in mice was shown to increase IL-33, a key cytokine in driving airway inflammation in asthma, but how IL-33 is regulated during viral infection remains unclear. We previously found that a genetic mutation in Toll-interacting protein (Tollip) was linked to less airway epithelial Tollip expression, increased neutrophil chemokines, and lower lung function in asthma patients. As Tollip is involved in maintaining mitochondrial function, and mitochondrial stress may contribute to extracellular ATP release and IL-33 secretion, we hypothesized that Tollip downregulates IL-33 secretion via inhibiting ATP release during IAV infection. Wild-type and Tollip knockout (KO) mice were infected with IAV and treated with either an ATP converter apyrase or an IL-33 decoy receptor soluble ST2 (sST2). KO mice significantly lost more body weight and had increased extracellular ATP, IL-33 release, and neutrophilic inflammation. Apyrase treatment reduced extracellular ATP levels, IL-33 release, and neutrophilic inflammation in Tollip KO mice. Excessive lung neutrophilic inflammation in IAV-infected Tollip KO mice was reduced by sST2, which was coupled with less IL-33 release. Our data suggest that Tollip inhibits IAV infection, potentially by inhibiting extracellular ATP release and reducing IL-33 activation and lung inflammation. In addition, sST2 may serve as a potential therapeutic approach to mitigate respiratory viral infection in human subjects with Tollip deficiency.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"67-77"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10643888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10317433","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

Acknowledgement to Reviewers 审稿人致谢

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2022-12-07 DOI: 10.1159/000527450

引用次数: 0

miR-142-5p Encapsulated by Serum-Derived Extracellular Vesicles Protects against Acute Lung Injury in Septic Rats following Remote Ischemic Preconditioning via the PTEN/PI3K/Akt Axis 经血清源性细胞外囊泡包封的miR-142-5p通过PTEN/PI3K/Akt轴保护脓毒症大鼠远程缺血预处理后的急性肺损伤

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2022-05-19 DOI: 10.1159/000522231

Wenliang Zhu, Xiaopei Huang, Shi-Yuan Qiu, Lingxiao Feng, Yue Wu, Huanzhang Shao

{"title":"miR-142-5p Encapsulated by Serum-Derived Extracellular Vesicles Protects against Acute Lung Injury in Septic Rats following Remote Ischemic Preconditioning via the PTEN/PI3K/Akt Axis","authors":"Wenliang Zhu, Xiaopei Huang, Shi-Yuan Qiu, Lingxiao Feng, Yue Wu, Huanzhang Shao","doi":"10.1159/000522231","DOIUrl":"https://doi.org/10.1159/000522231","url":null,"abstract":"This study intends to investigate the effects of miR-142-5p encapsulated by serum-derived extracellular vesicles (EVs) on septic acute lung injury (ALI) following remote ischemic preconditioning (RIPC) through a PTEN-involved mechanism. ALI was induced in rats by lipopolysaccharide (LPS) injection, 24 h before which RIPC was performed via the left lower limb. Next, the binding affinity between miR-142-5p and PTEN was identified. EVs were isolated from serum and injected into rats. The morphology of lung tissues, pulmonary edema, and inflammatory cell infiltration into lung tissues were then assessed, and TNF-α and IL-6 levels in serum and lung tissues were measured. The results indicated that RIPC could attenuate ALI in sepsis. miR-142-5p expression was increased in serum, lung tissues, and serum-derived EVs of ALI rats following RIPC. miR-142-5p could target PTEN to activate the PI3K/Akt signaling pathway. miR-142-5p shuttled by serum-derived EVs reduced pulmonary edema, neutrophil infiltration, and TNF-α and IL-6 levels, thus alleviating ALI in LPS-induced septic rats upon RIPC. Collectively, serum-derived EVs-loaded miR-142-5p downregulated PTEN and activated PI3K/Akt to inhibit ALI in sepsis following RIPC, thus highlighting potential therapeutic molecular targets against ALI in sepsis.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"14 1","pages":"532 - 542"},"PeriodicalIF":5.3,"publicationDate":"2022-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47767884","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: 1

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