Mareike D Maler, Sophie Zwick, Carsten Kallfass, Peggy Engelhard, Hexin Shi, Laura Hellig, Pang Zhengyang, Annika Hardt, Gernot Zissel, Zsolt Ruzsics, Willi Jahnen-Dechent, Stefan F Martin, Peter Jess Nielsen, Daiana Stolz, Justyna Lopatecka, Sarah Bastyans, Bruce Beutler, Wolfgang W Schamel, György Fejer, Marina Alexandra Freudenberg
{"title":"Type I Interferon, Induced by Adenovirus or Adenoviral Vector Infection, Regulates the Cytokine Response to Lipopolysaccharide in a Macrophage Type-Specific Manner.","authors":"Mareike D Maler, Sophie Zwick, Carsten Kallfass, Peggy Engelhard, Hexin Shi, Laura Hellig, Pang Zhengyang, Annika Hardt, Gernot Zissel, Zsolt Ruzsics, Willi Jahnen-Dechent, Stefan F Martin, Peter Jess Nielsen, Daiana Stolz, Justyna Lopatecka, Sarah Bastyans, Bruce Beutler, Wolfgang W Schamel, György Fejer, Marina Alexandra Freudenberg","doi":"10.1159/000538282","DOIUrl":"10.1159/000538282","url":null,"abstract":"<p><strong>Introduction: </strong>While TLR ligands derived from microbial flora and pathogens are important activators of the innate immune system, a variety of factors such as intracellular bacteria, viruses, and parasites can induce a state of hyperreactivity, causing a dysregulated and potentially life-threatening cytokine over-response upon TLR ligand exposure. Type I interferon (IFN-αβ) is a central mediator in the induction of hypersensitivity and is strongly expressed in splenic conventional dendritic cells (cDC) and marginal zone macrophages (MZM) when mice are infected with adenovirus. This study investigates the ability of adenoviral infection to influence the activation state of the immune system and underlines the importance of considering this state when planning the treatment of patients.</p><p><strong>Methods: </strong>Infection with adenovirus-based vectors (Ad) or pretreatment with recombinant IFN-β was used as a model to study hypersensitivity to lipopolysaccharide (LPS) in mice, murine macrophages, and human blood samples. The TNF-α, IL-6, IFN-αβ, and IL-10 responses induced by LPS after pretreatment were measured. Mouse knockout models for MARCO, IFN-αβR, CD14, IRF3, and IRF7 were used to probe the mechanisms of the hypersensitive reaction.</p><p><strong>Results: </strong>We show that, similar to TNF-α and IL-6 but not IL-10, the induction of IFN-αβ by LPS increases strongly after Ad infection. This is true both in mice and in human blood samples ex vivo, suggesting that the regulatory mechanisms seen in the mouse are also present in humans. In mice, the scavenger receptor MARCO on IFN-αβ-producing cDC and splenic marginal zone macrophages is important for Ad uptake and subsequent cytokine overproduction by LPS. Interestingly, not all IFN-αβ-pretreated macrophage types exposed to LPS exhibit an enhanced TNF-α and IL-6 response. Pretreated alveolar macrophages and alveolar macrophage-like murine cell lines (MPI cells) show enhanced responses, while bone marrow-derived and peritoneal macrophages show a weaker response. This correlates with the respective absence or presence of the anti-inflammatory IL-10 response in these different macrophage types. In contrast, Ad or IFN-β pretreatment enhances the subsequent induction of IFN-αβ in all macrophage types. IRF3 is dispensable for the LPS-induced IFN-αβ overproduction in infected MPI cells and partly dispensable in infected mice, while IRF7 is required. The expression of the LPS co-receptor CD14 is important but not absolutely required for the elicitation of a TNF-α over-response to LPS in Ad-infected mice.</p><p><strong>Conclusion: </strong>Viral infections or application of virus-based vaccines induces type I interferon and can tip the balance of the innate immune system in the direction of hyperreactivity to a subsequent exposure to TLR ligands. The adenoviral model presented here is one example of how multiple factors, both environmental and genetic, affect the physiological r","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"226-247"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11023693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288330","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}
Max Brendel, Thomas P Kohler, Janine V Neufend, Astrid Puppe, Nicolas Gisch, Sven Hammerschmidt
{"title":"Lipoteichoic Acids Are Essential for Pneumococcal Colonization and Membrane Integrity.","authors":"Max Brendel, Thomas P Kohler, Janine V Neufend, Astrid Puppe, Nicolas Gisch, Sven Hammerschmidt","doi":"10.1159/000539934","DOIUrl":"10.1159/000539934","url":null,"abstract":"<p><strong>Introduction: </strong>The hydrophilic, polymeric chain of the lipoteichoic acid (LTA) of the Gram-positive pathobiont Streptococcus pneumoniae is covalently linked to the glycosylglycerolipid α-<sc>d</sc>-glucopyranosyl-(1,3)-diacylglycerol by the LTA ligase TacL, leading to its fixation in the cytoplasmic membrane. Pneumococcal LTA, sharing identical repeating units with the wall teichoic acids (WTA), is dispensable for normal growth but required for full virulence in invasive infections.</p><p><strong>Methods: </strong>Mutants deficient in TacL and complemented strains constructed were tested for their growth, resistance against oxidative stress, and susceptibility against antimicrobial peptides. Further, the membrane fluidity of pneumococci, their capability to adhere to lung epithelial cells, and virulence in a Galleria mellonella as well as intranasal mouse infection model were assessed.</p><p><strong>Results: </strong>In the present study, we indicate that LTA is already indispensable for pneumococcal adherence to human nasopharyngeal cells and colonization in an intranasal mouse infection model. Mutants deficient for TacL did not show morphological defects. However, our analysis of pneumococcal membranes in different serotypes showed an altered membrane fluidity and surface protein abundance of lipoproteins in mutants deficient for LTA but not WTA. These mutants had a decreased membrane fluidity, exhibited higher amounts of lipoproteins, and showed an increased susceptibility to antimicrobial peptides. In complemented mutant strains, this defect was fully restored.</p><p><strong>Conclusion: </strong>Taken together, LTA is crucial for colonization and required to effectively protect pneumococci from innate immune defence mechanisms by maintaining the membrane integrity.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"370-384"},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432111","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}
Marcelo Teocchi, Thaís de Andrade Eugênio, Lia Furlaneto Marega, Isabella Quinti, Maria Marluce Dos Santos Vilela
{"title":"Dysregulation of Toll-Like Receptor Signaling-Associated Gene Expression in X-Linked Agammaglobulinemia: Implications for Correlations Genotype-Phenotype and Disease Expression.","authors":"Marcelo Teocchi, Thaís de Andrade Eugênio, Lia Furlaneto Marega, Isabella Quinti, Maria Marluce Dos Santos Vilela","doi":"10.1159/000540082","DOIUrl":"10.1159/000540082","url":null,"abstract":"<p><strong>Introduction: </strong>In X-linked agammaglobulinemia (XLA), the diversity of BTK variants complicates the study of genotype-phenotype correlations. Since BTK negatively regulates toll-like receptors (TLRs), we investigated if distinct BTK mutation types selectively modulate TLR pathways, affecting disease expression.</p><p><strong>Methods: </strong>Using reverse transcription-quantitative polymerase chain reaction, we quantified ten TLR signaling-related genes in XLA patients with missense (n = 3) and nonsense (n = 5) BTK mutations and healthy controls (n = 17).</p><p><strong>Results: </strong>BTK, IRAK2, PIK3R4, REL, TFRC, and UBE2N were predominantly downregulated, while RIPK2, TLR3, TLR10, and TLR6 showed variable regulation. The missense XLA group exhibited significant downregulation of IRAK2, PIK3R4, REL, and TFRC and upregulation of TLR3 and/or TLR6.</p><p><strong>Conclusion: </strong>Hypo-expression of TLR3, TLR6, and TLR10 may increase susceptibility to infections, while hyper-expression might contribute to chronic inflammatory conditions like arthritis or inflammatory bowel disease. Our findings shed light on the important inflammatory component characteristic of some XLA patients, even under optimal therapeutic conditions.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"425-439"},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906731","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}
Su Wang, Shufen Zhong, Ying Huang, Songling Zhu, Shuangfeng Chen, Ran Wang, Sonam Wangmo, Bo Peng, Houkun Lv, Jichao Yang, Liyan Ma, Zhiyang Ling, Yaguang Zhang, Pengfei Sui, Bing Sun
{"title":"MDM2 Is Essential to Maintain the Homeostasis of Epithelial Cells by Targeting p53.","authors":"Su Wang, Shufen Zhong, Ying Huang, Songling Zhu, Shuangfeng Chen, Ran Wang, Sonam Wangmo, Bo Peng, Houkun Lv, Jichao Yang, Liyan Ma, Zhiyang Ling, Yaguang Zhang, Pengfei Sui, Bing Sun","doi":"10.1159/000539824","DOIUrl":"10.1159/000539824","url":null,"abstract":"<p><strong>Introduction: </strong>MDM2 is known as the primary negative regulator of p53, and MDM2 promotes lung cancer fibrosis and lung injury through p53-dependent and p53-independent pathways. However, the mechanism by which MDM2 influences the pathogenesis of asthma is unknown. In this study, we investigated the function of MDM2 in lung epithelial cells in type 2 lung inflammation.</p><p><strong>Methods: </strong>We used type II alveolar epithelial cell-specific heterozygous knockout of Mdm2 mice to validate its function. Then papain-induced asthma model was established, and changes in inflammation were observed by measuring immunohistochemistry and flow cytometry analysis.</p><p><strong>Results: </strong>In this study, we knockdown the mouse Mdm2 gene in type 2 alveolar epithelial cells. We demonstrated that heterozygous Mdm2 gene-deleted mice were highly susceptible to protease allergen papain-induced pulmonary inflammation characterized by increased ILC2 numbers, IL-5 and IL-13 cytokine levels, and lung pathology. A mechanistic study showed that following the decreased expression of Mdm2 in lung epithelial cells and A549 cell line, p53 was overactivated, and the expression of its downstream genes p21, Puma, and Noxa was elevated, which resulted in apoptosis. After Mdm2 knockdown, the mRNA expression of inflammation-related gene IL-25, HMGB1, and TNF-α were increased, which further amplified the downstream ILC2 response and lung inflammation.</p><p><strong>Conclusion: </strong>These results indicate that Mdm2 maintains the homeostasis of lung epithelial cells by targeting P53 and regulates the function of lung epithelial cells under type 2 lung inflammation.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"397-412"},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971294","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 Neutrophil in COVID-19: Positive or Negative.","authors":"Na Rong, Xiaohui Wei, Jiangning Liu","doi":"10.1159/000535541","DOIUrl":"10.1159/000535541","url":null,"abstract":"<p><strong>Background: </strong>Neutrophils are the first line of defense against pathogens. They are divided into multiple subpopulations during development and kill pathogens through various mechanisms. Neutrophils are considered one of the markers of severe COVID-19.</p><p><strong>Summary: </strong>In-depth research has revealed that neutrophil subpopulations have multiple complex functions. Different subsets of neutrophils play an important role in the progression of COVID-19.</p><p><strong>Key messages: </strong>In this review, we provide a detailed overview of the developmental processes of neutrophils at different stages and their recruitment and activation after SARS-CoV-2 infection, aiming to elucidate the changes in neutrophil subpopulations, characteristics, and functions after infection and provide a reference for mechanistic research on neutrophil subpopulations in the context of SARS-CoV-2 infection. In addition, we have also summarized research progress on potential targeted drugs for neutrophil immunotherapy, hoping to provide information that aids the development of therapeutic drugs for the clinical treatment of critically ill COVID-19 patients.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"80-95"},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10861219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139472323","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}
Greg Haljan, Terry Lee, Anne McCarthy, Juthaporn Cowan, Jennifer Tsang, Francois Lelouche, Alexis F Turgeon, Patrick Archambault, Francois Lamontagne, Robert Fowler, Jennifer Yoon, Peter Daley, Matthew P Cheng, Donald C Vinh, Todd C Lee, Karen C Tran, Brent W Winston, Hyejin Julia Kong, John H Boyd, Keith R Walley, Allison McGeer, David M Maslove, John C Marshall, Joel Singer, Fagun Jain, James A Russell
{"title":"Complex Thrombo-Inflammatory Responses versus Outcomes of Non-COVID-19 Community-Acquired Pneumonia and COVID-19.","authors":"Greg Haljan, Terry Lee, Anne McCarthy, Juthaporn Cowan, Jennifer Tsang, Francois Lelouche, Alexis F Turgeon, Patrick Archambault, Francois Lamontagne, Robert Fowler, Jennifer Yoon, Peter Daley, Matthew P Cheng, Donald C Vinh, Todd C Lee, Karen C Tran, Brent W Winston, Hyejin Julia Kong, John H Boyd, Keith R Walley, Allison McGeer, David M Maslove, John C Marshall, Joel Singer, Fagun Jain, James A Russell","doi":"10.1159/000542420","DOIUrl":"10.1159/000542420","url":null,"abstract":"<p><strong>Introduction: </strong>The thrombo-inflammatory response and outcomes of community-acquired pneumonia (CAP) due to various organisms (non-COVID-19 CAP) versus CAP due to a single virus, SARS-CoV-2 (i.e., COVID-19) may differ.</p><p><strong>Methods: </strong>Adults hospitalized with non-COVID-19 CAP (December 1, 2021-June 15, 2023) or COVID-19 (March 2, 2020-June 15, 2023) in Canada. We compared non-COVID-19 CAP and COVID-19 baseline, thrombo-inflammatory response, and mortality. We measured plasma cytokine and coagulation factor levels in a sample of patients, did hierarchical clustering, and compared cytokine and coagulation factor levels.</p><p><strong>Results: </strong>In 2,485 patients (non-COVID-19 CAP, n = 719; COVID-19 patients, n = 2,157), non-COVID-19 CAP patients had significantly lower 28-day mortality (CAP vs. COVID-19 waves 1 and 2; 10% vs. 18% and 16%, respectively), intensive care unit admission (CAP vs. all waves; 15% vs. 39%, 37%, 33%, and 24%, respectively), invasive ventilation (CAP vs. waves 1, 2, and 3 patients; 11% vs. 25%, 20%, and 16%), vasopressor use (CAP 12% vs. 23%, 21%, and 18%), and renal replacement therapy use (CAP 3% vs. Omicron 7%). Complexity of hierarchical clustering aligned directly with mortality: COVID-19 wave 1 and 2 patients had six clusters at admission and higher mortality than non-COVID-19 CAP and Omicron that had three clusters at admission. Pooling all COVID-19 waves increased complexity with seven clusters on admission.</p><p><strong>Conclusion: </strong>Complex thrombo-inflammatory responses aligned with mortality of CAP. At a fundamental level, the human thrombo-inflammatory response to a brand new virus was \"confused\" whereas humans had eons of time to develop a more concise efficient thrombo-inflammatory host response to CAP.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"16 1","pages":"529-552"},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769550","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}
Zerick Terrell Dunbar, Salvador González-Ochoa, Thanigaivelan Kanagasabai, Alla Ivanova, Anil Shanker
{"title":"Differential Effector Function of Tissue-Specific Natural Killer Cells against Lung Tumors.","authors":"Zerick Terrell Dunbar, Salvador González-Ochoa, Thanigaivelan Kanagasabai, Alla Ivanova, Anil Shanker","doi":"10.1159/000542078","DOIUrl":"10.1159/000542078","url":null,"abstract":"<p><strong>Introduction: </strong>Natural killer (NK) cells are innate lymphoid cells capable of directly killing target cells while modulating immune effector responses. Despite their multifunctional capacities, a limited understanding of their plasticity and heterogeneity has impeded progress in developing effective NK cell-based cancer therapies. In this study, we investigated NK cell tissue heterogeneity in relation to their phenotype and effector functions against lung tumors.</p><p><strong>Methods: </strong>Using hanging drop tumor spheroid and subcutaneously established LL/2 (LLC1) lung tumor models, we examined NK cell receptor diversity and its correlation with tissue-specific cytotoxicity through multiparametric flow cytometry, fluorescence imaging, and cytotoxicity assays.</p><p><strong>Results: </strong>We identified distinct patterns of cell surface receptors expression on tissue-specific NK cells that are crucial for antitumor activity. Linear regression mathematical analyses further revealed significant positive correlations between activation-associated cell surface receptors and cytotoxic capacity in NK cells from tissues such as the liver and bone marrow.</p><p><strong>Conclusion: </strong>These findings underscore the differential effector capacities of NK cells from distinct tissues, even prior to exposure to LL/2 tumor cells. This highlights the significance of tissue-specific NK cell heterogeneity and its impact on their antitumor cytotoxicity. Recognizing these distinct tissue-specific receptor expression patterns will be instrumental in developing more efficacious NK cell-based cancer treatments.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"573-594"},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11644122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675984","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}
Abdulsalam Adegoke, Julia Hanson, Ryan C Smith, Shahid Karim
{"title":"Ehrlichia chaffeensis Co-Opts Phagocytic Hemocytes for Systemic Dissemination in the Lone Star Tick, Amblyomma americanum.","authors":"Abdulsalam Adegoke, Julia Hanson, Ryan C Smith, Shahid Karim","doi":"10.1159/000535986","DOIUrl":"10.1159/000535986","url":null,"abstract":"<p><strong>Introduction: </strong>Hematophagous arthropods can acquire and transmit several pathogens of medical importance. In ticks, the innate immune system is crucial in the outcome between vector-pathogen interaction and overall vector competence. However, the specific immune response(s) elicited by the immune cells known as hemocytes remains largely undefined in Ehrlichia chaffeensis and its competent tick vector, Amblyomma americanum.</p><p><strong>Methods: </strong>We utilized injection of clodronate liposome to deplete tick granulocytes combined with infection with E. chaffeensis to demonstrate their essential role in microbial infection.</p><p><strong>Results: </strong>Here, we show that granulocytes, professional phagocytic cells, are integral in eliciting immune responses against commensal and pathogen infection. The chemical depletion of granulocytes led to decreased phagocytic efficiency of tissue-associated hemocytes. We demonstrate that E. chaffeensis can infect circulating hemocytes, and both cell-free plasma and hemocytes from E. chaffeensis-infected ticks can establish Ehrlichia infection in recipient ticks. Lastly, we provide evidence to show that granulocytes play a dual role in E. chaffeensis infection. Depleting granulocytic hemocytes increased Ehrlichia load in the salivary gland and midgut tissues. In contrast, granulocyte depletion led to a reduced systemic load of Ehrlichia.</p><p><strong>Conclusion: </strong>This study has identified multiple roles for granulocytic hemocytes in the control and systemic dissemination of E. chaffeensis infection.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"66-79"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10794049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032400","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}
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}