Journal of Innate Immunity最新文献_第10页

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

Increase in the Complement Activation Product C4d and the Terminal Complement Complex sC5b-9 Is Associated with Disease Severity and a Fatal Outcome in Necrotizing Soft-Tissue Infection. 补体激活产物C4d和终末补体复合物sC5b-9的增加与坏死性软组织感染的疾病严重程度和致命结果相关

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2022-01-01 Epub Date: 2021-12-14 DOI: 10.1159/000520496

Morten Hedetoft, Martin Bruun Madsen, Cecilie Bo Hansen, Ole Hyldegaard, Peter Garred

{"title":"Increase in the Complement Activation Product C4d and the Terminal Complement Complex sC5b-9 Is Associated with Disease Severity and a Fatal Outcome in Necrotizing Soft-Tissue Infection.","authors":"Morten Hedetoft, Martin Bruun Madsen, Cecilie Bo Hansen, Ole Hyldegaard, Peter Garred","doi":"10.1159/000520496","DOIUrl":"https://doi.org/10.1159/000520496","url":null,"abstract":"The hyperinflammatory burden is immense in necrotizing soft-tissue infection (NSTI). The complement system is a key during the innate immune response and may be a promising target to reduce the inflammatory response, potentially improving the clinical outcome. However, complement activation and its association to disease severity and survival remain unknown in NSTI. Therefore, we prospectively enrolled patients with NSTI and sampled blood at admission and once daily for the following 3 days. Plasma C4c, C4d, C3bc, and C3dg and the terminal complement complex (TCC) were evaluated using ELISA techniques. In total, 242 patients were included with a median age of 62 years, with a 60% male predominance. All-cause 30-day mortality was 17% (95% confidence interval [CI] 13-23) with a follow-up of >98%. C4c and C3dg were negatively correlated with Simplified Acute Physiology Score II (Rho -0.22, p < 0.001 and Rho -0.17, p = 0.01). Patients with septic shock (n = 114, 47%) had higher levels of baseline TCC than those in non-shock patients (18 vs. 14, p < 0.001). TCC correlated with the Sequential Organ Failure Assessment (SOFA) score (Rho 0.19, p = 0.004). In multivariate Cox regression analysis (adjusted for age, sex, comorbidity, and SOFA score), high baseline C4d (>20 ng/mL) and the combination of high C4d and TCC (>31 arbitrary units/mL) were associated with increased 30-day mortality (hazard ratio [HR] 3.26, 95% CI 1.56-6.81 and HR 5.12, 95% CI 2.15-12.23, respectively). High levels of both C4d and TCC demonstrated a negative predictive value of 0.87. In conclusion, we found that in patients with NSTI, complement activation correlated with the severity of the disease. High baseline C4d and combination of high C4d and TCC are associated with increased 30-day mortality. Low baseline C4d or TCC indicates a higher probability of survival.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"14 4","pages":"355-365"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39835124","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

GDF15 Suppresses Lymphoproliferation and Humoral Autoimmunity in a Murine Model of Systemic Lupus Erythematosus. GDF15抑制系统性红斑狼疮小鼠模型的淋巴细胞增殖和体液自身免疫。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2022-01-01 DOI: 10.1159/000523991

Georg Lorenz, Andrea Ribeiro, Ekatharina von Rauchhaupt, Vivian Würf, Christoph Schmaderer, Clemens D Cohen, Twinkle Vohra, Hans-Joachim Anders, Maja Lindenmeyer, Maciej Lech

{"title":"GDF15 Suppresses Lymphoproliferation and Humoral Autoimmunity in a Murine Model of Systemic Lupus Erythematosus.","authors":"Georg Lorenz, Andrea Ribeiro, Ekatharina von Rauchhaupt, Vivian Würf, Christoph Schmaderer, Clemens D Cohen, Twinkle Vohra, Hans-Joachim Anders, Maja Lindenmeyer, Maciej Lech","doi":"10.1159/000523991","DOIUrl":"https://doi.org/10.1159/000523991","url":null,"abstract":"Growth and differentiation factor 15 (GDF15), a divergent member of the transforming growth factor-β superfamily, has been associated with acute and chronic inflammatory conditions including autoimmune disease, i.e., type I diabetes and rheumatoid arthritis. Still, its role in systemic autoimmune disease remains elusive. Thus, we studied GDF15-deficient animals in Fas-receptor intact (C57BL/6) or deficient (C57BL/6lpr/lpr) backgrounds. Further, lupus nephritis (LN) microdissected kidney biopsy specimens were analyzed to assess the involvement of GDF15 in human disease. GDF15-deficiency in lupus-prone mice promoted lymphoproliferation, T-, B- and plasma cell-expansion, a type I interferon signature, and increased serum levels of anti-DNA autoantibodies. Accelerated systemic inflammation was found in association with a relatively mild renal phenotype. Splenocytes of phenotypically overall-normal Gdf15-/- C57BL/6 and lupus-prone C57BL/6lpr/lpr mice displayed increased in vitro lymphoproliferative responses or interferon-dependent transcription factor induction in response to the toll-like-receptor (TLR)-9 ligand CpG, or the TLR-7 ligand Imiquimod, respectively. In human LN, GDF15 expression was downregulated whereas type I interferon expression was upregulated in glomerular- and tubular-compartments versus living donor controls. These findings demonstrate that GDF15 regulates lupus-like autoimmunity by suppressing lymphocyte-proliferation and -activation. Further, the data indicate a negative regulatory role for GDF15 on TLR-7 and -9 driven type I interferon signaling in effector cells of the innate immune system.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"14 6","pages":"673-689"},"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/30/92/jin-0014-0673.PMC9801254.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10454306","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: 4

Regulation of TLR10 Expression and Its Role in Chemotaxis of Human Neutrophils. TLR10表达调控及其在人中性粒细胞趋化中的作用。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2022-01-01 DOI: 10.1159/000524461

Yadu Balachandran, Sarah Caldwell, Gurpreet Kaur Aulakh, Baljit Singh

{"title":"Regulation of TLR10 Expression and Its Role in Chemotaxis of Human Neutrophils.","authors":"Yadu Balachandran, Sarah Caldwell, Gurpreet Kaur Aulakh, Baljit Singh","doi":"10.1159/000524461","DOIUrl":"https://doi.org/10.1159/000524461","url":null,"abstract":"Toll-like receptors are innate immune receptors that play a critical role in pathogen-associated molecular pattern recognition. TLR10 was recently identified and very limited data are available on its expression, mechanisms that regulate its expression, and its role in primary immune cells. To study the expression pattern of TLR10 in primary immune cells, we examined TLR10 protein expression in naive and Escherichia coli lipopolysaccharide (LPS)-activated human neutrophils. Human neutrophils challenged with LPS showed a decrease in total and surface TLR10 expression at 90 min. TLR10 in LPS-activated neutrophils colocalized with flotallin-1, a lipid raft marker, and EEA-1, an early endosomal marker, to suggest its endocytosis. There was increased colocalization of TLR10 with TLR4 at LPS 60 min followed by decrease at later LPS treatment times. Treatment with TLR4 neutralizing antibody decreased cytoplasmic localization of TLR10 in LPS-treated neutrophils. Reactive oxygen species (ROS) depletion and neutralization of p65 subunit of NF-κB in LPS-treated neutrophils decreased TLR10 expression. Live cell imaging of LPS-activated neutrophils showed TLR10 translocation in the leading edge and TLR10 knockdown in neutrophils reduced their fMLP-induced chemotaxis and the number of neutrophils with pseudopodia but without affecting the expression of key proteins of actin nucleation process, ARP-3 and Diap1. Taken together, our findings show that neutrophil activation alters TLR10 expression through ROS production and NF-κB regulation, and TLR10 knockdown reduced neutrophil chemotaxis.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"14 6","pages":"629-642"},"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/22/c5/jin-0014-0629.PMC9801258.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10459543","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

Porphyromonas gingivalis Gingipains-Mediated Degradation of Plasminogen Activator Inhibitor-1 Leads to Delayed Wound Healing Responses in Human Endothelial Cells. 牙龈卟啉单胞菌介导的纤溶酶原激活物抑制剂-1降解导致人内皮细胞伤口愈合反应延迟。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2022-01-01 Epub Date: 2021-11-25 DOI: 10.1159/000519737

Li-Ting Song, Hiroyuki Tada, Takashi Nishioka, Eiji Nemoto, Takahisa Imamura, Jan Potempa, Chang-Yi Li, Kenji Matsushita, Shunji Sugawara

{"title":"Porphyromonas gingivalis Gingipains-Mediated Degradation of Plasminogen Activator Inhibitor-1 Leads to Delayed Wound Healing Responses in Human Endothelial Cells.","authors":"Li-Ting Song, Hiroyuki Tada, Takashi Nishioka, Eiji Nemoto, Takahisa Imamura, Jan Potempa, Chang-Yi Li, Kenji Matsushita, Shunji Sugawara","doi":"10.1159/000519737","DOIUrl":"https://doi.org/10.1159/000519737","url":null,"abstract":"Plasminogen activator inhibitor-1 (PAI-1), a serine protease inhibitor, is constitutively produced by endothelial cells and plays a vital role in maintaining vascular homeostasis. Chronic periodontitis is an inflammatory disease characterized by bleeding of periodontal tissues that support the tooth. In this study, we aimed to determine the role of PAI-1 produced by endothelial cells in response to infections caused by the primary periodontal pathogen Porphyromonas gingivalis. We demonstrated that P. gingivalis infection resulted in significantly reduced PAI-1 levels in human endothelial cells. This reduction in PAI-1 levels could be attributed to the proteolysis of PAI-1 by P. gingivalis proteinases, especially lysine-specific gingipain-K (Kgp). We demonstrated the roles of these degradative enzymes in the endothelial cells using a Kgp-specific inhibitor and P. gingivalis gingipain-null mutants, in which the lack of the proteinases resulted in the absence of PAI-1 degradation. The degradation of PAI-1 by P. gingivalis induced a delayed wound healing response in endothelial cell layers via the low-density lipoprotein receptor-related protein. Our results collectively suggested that the proteolysis of PAI-1 in endothelial cells by gingipains of P. gingivalis might lead to the deregulation of endothelial homeostasis, thereby contributing to the permeabilization and dysfunction of the vascular endothelial barrier.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"14 4","pages":"306-319"},"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/52/fa/jin-0014-0306.PMC9275039.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39658706","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: 6

IL-1 Mediates Tissue-Specific Inflammation and Severe Respiratory Failure in COVID-19. IL-1介导COVID-19组织特异性炎症和严重呼吸衰竭

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2022-01-01 DOI: 10.1159/000524560

Georgios Renieris, Eleni Karakike, Theologia Gkavogianni, Dionysia-Eirini Droggiti, Emmanouil Stylianakis, Theano Andriopoulou, Victoria-Marina Spanou, Dionyssios Kafousopoulos, Mihai G Netea, Jesper Eugen-Olsen, John Simard, Evangelos J Giamarellos-Bourboulis

{"title":"IL-1 Mediates Tissue-Specific Inflammation and Severe Respiratory Failure in COVID-19.","authors":"Georgios Renieris, Eleni Karakike, Theologia Gkavogianni, Dionysia-Eirini Droggiti, Emmanouil Stylianakis, Theano Andriopoulou, Victoria-Marina Spanou, Dionyssios Kafousopoulos, Mihai G Netea, Jesper Eugen-Olsen, John Simard, Evangelos J Giamarellos-Bourboulis","doi":"10.1159/000524560","DOIUrl":"https://doi.org/10.1159/000524560","url":null,"abstract":"Acute respiratory distress syndrome (ARDS) in COVID-19 has been associated with catastrophic inflammation. We present measurements in humans and a new animal model implicating a role in danger-associated molecular patterns. Calprotectin (S100A8/A9) and high-mobility group box 1 (HMGB1) were measured in patients without/with ARDS, and admission calprotectin was associated with soluble urokinase plasminogen activator receptor (suPAR). An animal model was developed by intravenous injection of plasma from healthy or patients with COVID-19 ARDS into C57/BL6 mice once daily for 3 consecutive days. Mice were treated with one anti-S100A8/A9 antibody, the IL-1 receptor antagonist anakinra or vehicle, and Flo1-2a anti-murine anti-IL-1α monoclonal antibody or the specific antihuman IL-1α antibody XB2001 or isotype controls. Cytokines and myeloperoxidase (MPO) were measured in tissues. Calprotectin, but not HMGB1, was elevated in ARDS. Higher suPAR indicated higher calprotectin. Animal challenge with COVID-19 plasma led to inflammatory reactions in murine lung and intestines as evidenced by increased levels of TNFα, IL-6, IFNγ, and MPO. Lung inflammation was attenuated with anti-S100A8/A9 pre-treatment. Anakinra treatment restored these levels. Similar decrease was found in mice treated with Flo1-2a but not with XB2001. Circulating alarmins, specifically calprotectin, of critically ill COVID-19 patients induces tissue-specific inflammatory responses through an IL-1-mediated mechanism. This could be attenuated through inhibition of IL-1 receptor or of IL-1α.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"14 6","pages":"643-656"},"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/93/69/jin-0014-0643.PMC9801253.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10447282","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: 16

Broad Ultrastructural and Transcriptomic Changes Underlie the Multinucleated Giant Hemocyte Mediated Innate Immune Response against Parasitoids. 广泛的超微结构和转录组变化是多核巨血细胞介导的先天性免疫应答对类寄生物的影响。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2022-01-01 Epub Date: 2021-12-03 DOI: 10.1159/000520110

Gyöngyi Cinege, Lilla B Magyar, Attila L Kovács, Zita Lerner, Gábor Juhász, David Lukacsovich, Jochen Winterer, Tamás Lukacsovich, Zoltán Hegedűs, Éva Kurucz, Dan Hultmark, Csaba Földy, István Andó

{"title":"Broad Ultrastructural and Transcriptomic Changes Underlie the Multinucleated Giant Hemocyte Mediated Innate Immune Response against Parasitoids.","authors":"Gyöngyi Cinege, Lilla B Magyar, Attila L Kovács, Zita Lerner, Gábor Juhász, David Lukacsovich, Jochen Winterer, Tamás Lukacsovich, Zoltán Hegedűs, Éva Kurucz, Dan Hultmark, Csaba Földy, István Andó","doi":"10.1159/000520110","DOIUrl":"https://doi.org/10.1159/000520110","url":null,"abstract":"Multinucleated giant hemocytes (MGHs) represent a novel type of blood cell in insects that participate in a highly efficient immune response against parasitoid wasps involving isolation and killing of the parasite. Previously, we showed that circulating MGHs have high motility and the interaction with the parasitoid rapidly triggers encapsulation. However, structural and molecular mechanisms behind these processes remained elusive. Here, we used detailed ultrastructural analysis and live cell imaging of MGHs to study encapsulation in Drosophila ananassae after parasitoid wasp infection. We found dynamic structural changes, mainly driven by the formation of diverse vesicular systems and newly developed complex intracytoplasmic membrane structures, and abundant generation of giant cell exosomes in MGHs. In addition, we used RNA sequencing to study the transcriptomic profile of MGHs and activated plasmatocytes 72 h after infection, as well as the uninduced blood cells. This revealed that differentiation of MGHs was accompanied by broad changes in gene expression. Consistent with the observed structural changes, transcripts related to vesicular function, cytoskeletal organization, and adhesion were enriched in MGHs. In addition, several orphan genes encoding for hemolysin-like proteins, pore-forming toxins of prokaryotic origin, were expressed at high level, which may be important for parasitoid elimination. Our results reveal coordinated molecular and structural changes in the course of MGH differentiation and parasitoid encapsulation, providing a mechanistic model for a powerful innate immune response.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"14 4","pages":"335-354"},"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/71/de/jin-0014-0335.PMC9275024.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39691651","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: 1