Yanqin Du, Hang Sun, Sonakshi Bhattacharjee, Alexander Birkmann, Ulf Dittmer, Mengji Lu
{"title":"TLR9-Dependent Activation by Inactivated Parapoxvirus Ovis in Murine Bone Marrow-Derived Dendritic Cells Is Associated with Specific Strain-Dependent Dendritic Cell Subsets.","authors":"Yanqin Du, Hang Sun, Sonakshi Bhattacharjee, Alexander Birkmann, Ulf Dittmer, Mengji Lu","doi":"10.1159/000538625","DOIUrl":"10.1159/000538625","url":null,"abstract":"<p><strong>Introduction: </strong>Inactivated parapoxvirus ovis (iPPVO) exerts strong immunomodulatory effects on innate immune cells, making it an attractive therapeutic candidate. However, little is known about the signaling pathways that are involved in iPPVO-induced immune responses.</p><p><strong>Methods: </strong>In this study, we systematically analyzed how different types of dendritic cells (DCs) react to iPPVO (Zylexis, strain D1701) in both BALB/c and C57BL/6 mice by flow cytometry and ELISAs, and investigated which signaling pathway is related to DC activation by Western blotting and protein profiling.</p><p><strong>Results: </strong>We demonstrated that bone marrow-derived conventional DCs (BM-cDCs) and bone marrow-derived plasmacytoid DCs (BM-pDCs) matured and secreted type I interferons in response to Zylexis stimulation in both mouse strains. Similarly, Zylexis promoted the secretion of IL-12/23p40 and TNF by pDCs. However, IL-12/23p40 and TNF secretion by cDCs were induced in BALB/c mice but not in C57BL/6 mice. Analyzing the underlying signaling pathways revealed that iPPVO-induced maturation of cDCs was Toll-like receptor 9 (TLR9) independent, while the maturation of pDCs partially depended on the TLR9 pathway. Moreover, the production of proinflammatory cytokines by cDCs and the secretion of IFN-α/β by pDCs partially depended on the TLR9 pathway in both mouse strains. Therefore, other signaling pathways seem to participate in the response of DCs to iPPVO, supported by protein profiling.</p><p><strong>Conclusion: </strong>Our data provide useful insights into the diversity of iPPVO sensors and their varying effects across different strains and species.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"354-366"},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11249554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296214","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}
{"title":"Obituary of Prof. Uli Theopold, 1957-2023.","authors":"Ylva Engström, Bruno Lemaitre, Dan Hultmark","doi":"10.1159/000535642","DOIUrl":"10.1159/000535642","url":null,"abstract":"","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"16 1","pages":"31-32"},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10773639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667484","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}
{"title":"The Role of Ficolins in Lung Injury.","authors":"Meiyun Zhao, Xiaowu Tan, Xu Wu","doi":"10.1159/000540954","DOIUrl":"10.1159/000540954","url":null,"abstract":"<p><strong>Background: </strong>Respiratory diseases seriously threaten human health worldwide, and lung injury is an important component of respiratory disease. Complement activation is an important function of the innate immune system. Complement activation helps the body defend against invasion by external microorganisms, whereas excessive complement activation can exacerbate tissue damage or lead to unwanted side effects. Ficolins are a class of immune-related proteins in the lectin pathway that play important roles in the body's immune defense. Although individual ficolins are not well understood, current information suggests that ficolins may play an important regulatory role in lung injury.</p><p><strong>Summary: </strong>Several studies have shown that ficolins are involved in the immune response in the lung, particularly in the response to infectious and inflammatory processes.</p><p><strong>Key messages: </strong>This review summarizes the role of ficolins in lung injury. Ficolins may influence the development and repair of lung injury by recognizing and binding pathogenic microorganisms, modulating the inflammatory response, and promoting the clearance of immune cells. In addition, ficolins are associated with the development and progression of lung diseases (such as pneumonia and ARDS) and may have an important impact on the pathophysiological processes of inflammatory diseases.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"440-450"},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006268","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}
Beatrice Fageräng, Maximilian Peter Götz, Leon Cyranka, Corinna Lau, Per H Nilsson, Tom Eirik Mollnes, Peter Garred
{"title":"The Inflammatory Response Induced by Aspergillus fumigatus Conidia Is Dependent on Complement Activation: Insight from a Whole Blood Model.","authors":"Beatrice Fageräng, Maximilian Peter Götz, Leon Cyranka, Corinna Lau, Per H Nilsson, Tom Eirik Mollnes, Peter Garred","doi":"10.1159/000539368","DOIUrl":"10.1159/000539368","url":null,"abstract":"<p><strong>Introduction: </strong>We aimed to elucidate the inflammatory response of Aspergillus fumigatus conidia in a whole-blood model of innate immune activation and to compare it with the well-characterized inflammatory reaction to Escherichia coli.</p><p><strong>Methods: </strong>Employing a human lepirudin whole-blood model, we analyzed complement and leukocyte activation by measuring the sC5b-9 complex and assessing CD11b expression. A 27-multiplex system was used for quantification of cytokines. Selective cell removal from whole blood and inhibition of C3, C5, and CD14 were also applied.</p><p><strong>Results: </strong>Our findings demonstrated a marked elevation in sC5b-9 and CD11b post-A. fumigatus incubation. Thirteen cytokines (TNF, IL-1β, IL-1ra, IL-4, IL-6, IL-8, IL-17, IFNγ, MCP-1, MIP-1α, MIP-1β, FGF-basic, and G-CSF) showed increased levels. A generally lower level of cytokine release and CD11b expression was observed with A. fumigatus conidia than with E. coli. Notably, monocytes were instrumental in releasing all cytokines except MCP-1. IL-1ra was found to be both monocyte and granulocyte-dependent. Pre-inhibiting with C3 and CD14 inhibitors resulted in decreased release patterns for six cytokines (TNF, IL-1β, IL-6, IL-8, MIP-1α, and MIP-1β), with minimal effects by C5-inhibition.</p><p><strong>Conclusion: </strong>A. fumigatus conidia induced complement activation comparable to E. coli, whereas CD11b expression and cytokine release were lower, underscoring distinct inflammatory responses between these pathogens. Complement C3 inhibition attenuated cytokine release indicating a C3-level role of complement in A. fumigatus immunity.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"324-336"},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11250388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071264","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}
{"title":"Analyzing the Role of Specific Damage-Associated Molecular Patterns-Related Genes in Osteoarthritis and Investigating the Association between β-Amyloid and Apolipoprotein E Isoforms.","authors":"Fangling Yuan, Yatian Tang, Feifei Zheng, Qipeng Xie","doi":"10.1159/000541542","DOIUrl":"10.1159/000541542","url":null,"abstract":"<p><strong>Introduction: </strong>Osteoarthritis (OA) is a prevalent chronic joint disorder. It is characterized by an immune response that maintains a low level of inflammation throughout its progression. During OA, cartilage degradation leads to the release of damage-associated molecular patterns (DAMPs), which intensify the inflammatory response. β-Amyloid is a well-recognized DAMP in OA, can interact with APOE isoforms.</p><p><strong>Methods: </strong>This study identified DAMPs-related genes in OA using bioinformatics techniques. Additionally, we examined the expression levels of β-amyloid and apolipoprotein E (ApoE) isoforms by enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>We identified 10 key genes by machine learning techniques. Immune infiltration analysis revealed upregulation of various immune cell types in OA cartilage, underscoring the critical role of inflammation in OA pathogenesis. In the validation study, elevated serum levels of β-amyloid in knee osteoarthritis (KOA) patients were confirmed, showing positive correlations with ApoE2 and ApoE4. Notably, ApoE3 was identified as an independent protective factor against KOA.</p><p><strong>Conclusion: </strong>In this bioinformatics analysis, we identified the DAMPs-related genes of KOA and explored their potential functions and regulatory networks. The high expression of β-amyloid in KOA was confirmed by experiments, and the correlation between β-amyloid and ApoE2, ApoE4 in KOA was revealed for the first time, this provides a new way to explore the pathogenesis of KOA and to study the therapeutic targets of KOA.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"16 1","pages":"501-512"},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545924","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}
Min Feng, Shigang Fei, Jinglei Zou, Junming Xia, Wenxuan Lai, Yigui Huang, Luc Swevers, Jingchen Sun
{"title":"Single-Nucleus Sequencing of Silkworm Larval Brain Reveals the Key Role of Lysozyme in the Antiviral Immune Response in Brain Hemocytes.","authors":"Min Feng, Shigang Fei, Jinglei Zou, Junming Xia, Wenxuan Lai, Yigui Huang, Luc Swevers, Jingchen Sun","doi":"10.1159/000537815","DOIUrl":"10.1159/000537815","url":null,"abstract":"<p><strong>Introduction: </strong>The brain is considered as an immune-privileged organ, yet innate immune reactions can occur in the central nervous system of vertebrates and invertebrates. Silkworm (Bombyx mori) is an economically important insect and a lepidopteran model species. The diversity of cell types in the silkworm brain, and how these cell subsets produce an immune response to virus infection, remains largely unknown.</p><p><strong>Methods: </strong>Single-nucleus RNA sequencing (snRNA-seq), bioinformatics analysis, RNAi, and other methods were mainly used to analyze the cell types and gene functions of the silkworm brain.</p><p><strong>Results: </strong>We used snRNA-seq to identify 19 distinct clusters representing Kenyon cell, glial cell, olfactory projection neuron, optic lobes neuron, hemocyte-like cell, and muscle cell types in the B. mori nucleopolyhedrovirus (BmNPV)-infected and BmNPV-uninfected silkworm larvae brain at the late stage of infection. Further, we found that the cell subset that exerts an antiviral function in the silkworm larvae brain corresponds to hemocytes. Specifically, antimicrobial peptides were significantly induced by BmNPV infection in the hemocytes, especially lysozyme, exerting antiviral effects.</p><p><strong>Conclusion: </strong>Our single-cell dataset reveals the diversity of silkworm larvae brain cells, and the transcriptome analysis provides insights into the immune response following virus infection at the single-cell level.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"173-187"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10965234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931524","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}
{"title":"Macrophage: Hidden Criminal in Therapy Resistance.","authors":"Yimin Ding, Qian Cao, Wenjuan Yang, Junjie Xu, Peng Xiao","doi":"10.1159/000538212","DOIUrl":"10.1159/000538212","url":null,"abstract":"<p><strong>Background: </strong>Although substantial efforts have been made by researchers to develop drugs, a disappointing reality is that the emergence of drug resistance is an unavoidable reality for the majority of patients. In recent years, emerging evidence suggests a connection between drug resistance and immune dysregulation.</p><p><strong>Summary: </strong>As a ubiquitously distributed, versatile innate immune cell, macrophages play essential roles in maintaining tissue homeostasis in a steady state. Nevertheless, it is becoming aware that macrophages undermine the action of therapeutic drugs across various disease types. Reprogramming macrophage function has been proven to be effective in restoring patient responsiveness to treatment. Herein, we comprehensively reviewed how macrophages respond to drugs and the mechanisms by which they contribute to treatment unresponsiveness in cancer, inflammatory diseases, and metabolic diseases. In addition, future prospects in macrophage-based combination therapy were discussed.</p><p><strong>Key messages: </strong>Targeting macrophages is a promising strategy for overcoming drug resistance in immune disorders.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"188-202"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10990480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039581","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}
{"title":"The Roles of Innate Immune Cells in Atopic Dermatitis.","authors":"Yuke Pan, Youyi Wang, Meinian Xu, Meizhen Zhong, Xiaoming Peng, Kang Zeng, Xiaowen Huang","doi":"10.1159/000539534","DOIUrl":"10.1159/000539534","url":null,"abstract":"<p><strong>Background: </strong>Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by recurrent eczematous lesions and severe pruritus. The economic burden and time penalty caused by the relapse of AD reduce patients' life quality.</p><p><strong>Summary: </strong>AD has complex pathogenesis, including genetic disorders, epidermal barrier dysfunction, abnormal immune responses, microbial dysbiosis of the skin, and environmental factors. Recently, the role of innate immune cells in AD has attracted considerable attention. This review highlighted recent findings on innate immune cells in the onset and progression of AD.</p><p><strong>Key messages: </strong>Innate immune cells play essential roles in the pathogenesis of AD and enough attention should be given for treating AD from the perspective of innate immunity in clinics.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"385-396"},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723775","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}
Anthony Altieri, Courtney Lynn Marshall, Padmanie Ramotar, Dylan Lloyd, Mahadevappa Hemshekhar, Victor Spicer, Anne M van der Does, Neeloffer Mookherjee
{"title":"Human Host Defense Peptide LL-37 Suppresses TNFα-Mediated Matrix Metalloproteinases MMP9 and MMP13 in Human Bronchial Epithelial Cells.","authors":"Anthony Altieri, Courtney Lynn Marshall, Padmanie Ramotar, Dylan Lloyd, Mahadevappa Hemshekhar, Victor Spicer, Anne M van der Does, Neeloffer Mookherjee","doi":"10.1159/000537775","DOIUrl":"10.1159/000537775","url":null,"abstract":"<p><strong>Introduction: </strong>TNFα-inducible matrix metalloproteinases play a critical role in the process of airway remodeling in respiratory inflammatory disease including asthma. The cationic host defense peptide LL-37 is elevated in the lungs during airway inflammation. However, the impact of LL-37 on TNFα-driven processes is not well understood. Here, we examined the effect of LL-37 on TNFα-mediated responses in human bronchial epithelial cells (HBECs).</p><p><strong>Methods: </strong>We used a slow off-rate modified aptamer-based proteomics approach to define the HBEC proteome altered in response to TNFα. Abundance of selected protein candidates and signaling intermediates was examined using immunoassays, ELISA and Western blots, and mRNA abundance was examined by qRT-PCR.</p><p><strong>Results: </strong>Proteomics analysis revealed that 124 proteins were significantly altered, 12 proteins were enhanced by ≥2-fold compared to unstimulated cells, in response to TNFα. MMP9 was the topmost increased protein in response to TNFα, enhanced by ∼10-fold, and MMP13 was increased by ∼3-fold, compared to unstimulated cells. Furthermore, we demonstrated that LL-37 significantly suppressed TNFα-mediated MMP9 and MMP13 in HBEC. Mechanistic data revealed that TNFα-mediated MMP9 and MMP13 production is controlled by SRC kinase and that LL-37 enhances related upstream negative regulators, namely, phospho-AKT (T308) and TNFα-mediated TNFAIP3 or A20.</p><p><strong>Conclusions: </strong>The findings of this study suggest that LL-37 may play a role in intervening in the process of airway remodeling in chronic inflammatory respiratory disease such as asthma.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"203-215"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140110421","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}
Jose R Pittaluga, Federico Birnberg-Weiss, Agustina Serafino, Joselyn E Castro, Luis A Castillo, Daiana Martire-Greco, Paula Barrionuevo, Gabriela C Fernández, Verónica I Landoni
{"title":"The RNA from Pseudomonas aeruginosa Reduces Neutrophil Responses Favoring Bacterial Survival.","authors":"Jose R Pittaluga, Federico Birnberg-Weiss, Agustina Serafino, Joselyn E Castro, Luis A Castillo, Daiana Martire-Greco, Paula Barrionuevo, Gabriela C Fernández, Verónica I Landoni","doi":"10.1159/000541414","DOIUrl":"10.1159/000541414","url":null,"abstract":"<p><strong>Introduction: </strong>Epithelial and endothelial cells modulate innate immune responses in the lung, including the arrival of neutrophils (PMN), which are crucial cells for the antibacterial host defense. Cells are exposed to prokaryotic RNA (pRNA) during bacterial infections and different pRNA may promote or attenuate the inflammatory response on different immune cells. Pseudomonas aeruginosa (PAE) can cause severe pneumonia and has several immune-evading mechanisms. The aim of this study was to determine the effects of the RNA from PAE (RNAPAE) on lung epithelial, endothelial cells, and PMN, and its impact on bacterial elimination.</p><p><strong>Methods: </strong>Purified total RNAPAE was used as a stimulus on a human lung epithelial cell line (Calu-6), human microvascular endothelial cell line HMEC-1 and isolated healthy human PMN. Activation and cytokine secretion were evaluated. In addition, PMN elimination of live ECO or PAE was determined in the presence of RNAPAE.</p><p><strong>Results: </strong>We found that RNAPAE either induced a pro-inflammatory response on Calu-6 and HMEC-1 or PMN. Pre-stimulation of PMN with RNAPAE diminished activation and chemotaxis induced by live bacteria. Moreover, we found that RNAPAE reduced phagocytosis of live ECO. Finally, we also found that non-degraded fragments of small RNA (<200 bp) were responsible for the PMN microbicidal attenuation during PAE elimination.</p><p><strong>Conclusion: </strong>Our results indicated that short fragments of RNAPAE diminished the immune response of PMN favoring bacterial survival.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"489-500"},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289292","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}