Journal of Innate Immunity最新文献_第8页

Tryptophol Acetate and Tyrosol Acetate, Small-Molecule Metabolites Identified in a Probiotic Mixture, Inhibit Hyperinflammation. 在益生菌混合物中发现的小分子代谢物乙酸色醇酯和乙酸酪醇酯可抑制炎症反应。

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-02-21 DOI: 10.1159/000529782

Orit Malka, Ravit Malishev, Marina Bersudsky, Manikandan Rajendran, Mathumathi Krishnamohan, Jakeer Shaik, Daniel A Chamovitz, Evgeni Tikhonov, Eliya Sultan, Omry Koren, Ron N Apte, Benyamin Rosental, Elena Voronov, Raz Jelinek

{"title":"Tryptophol Acetate and Tyrosol Acetate, Small-Molecule Metabolites Identified in a Probiotic Mixture, Inhibit Hyperinflammation.","authors":"Orit Malka, Ravit Malishev, Marina Bersudsky, Manikandan Rajendran, Mathumathi Krishnamohan, Jakeer Shaik, Daniel A Chamovitz, Evgeni Tikhonov, Eliya Sultan, Omry Koren, Ron N Apte, Benyamin Rosental, Elena Voronov, Raz Jelinek","doi":"10.1159/000529782","DOIUrl":"10.1159/000529782","url":null,"abstract":"Probiotic fermented foods are perceived as contributing to human health; however, solid evidence for their presumptive therapeutic systemic benefits is generally lacking. Here we report that tryptophol acetate and tyrosol acetate, small-molecule metabolites secreted by the probiotic milk-fermented yeast Kluyveromyces marxianus, inhibit hyperinflammation (e.g., \"cytokine storm\"). Comprehensive in vivo and in vitro analyses, employing LPS-induced hyperinflammation models, reveal dramatic effects of the molecules, added in tandem, on mice morbidity, laboratory parameters, and mortality. Specifically, we observed attenuated levels of the proinflammatory cytokines IL-6, IL-1α, IL-1β, and TNF-α and reduced reactive oxygen species. Importantly, tryptophol acetate and tyrosol acetate did not completely suppress proinflammatory cytokine generation, rather brought their concentrations back to baseline levels, thus maintaining core immune functions, including phagocytosis. The anti-inflammatory effects of tryptophol acetate and tyrosol acetate were mediated through downregulation of TLR4, IL-1R, and TNFR signaling pathways and increased A20 expression, leading to NF-kB inhibition. Overall, this work illuminates phenomenological and molecular details underscoring anti-inflammatory properties of small molecules identified in a probiotic mixture, pointing to potential therapeutic avenues against severe inflammation.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"531-547"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10315057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10101109","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

Development, Characterization, and in vivo Validation of a Humanized C6 Monoclonal Antibody that Inhibits the Membrane Attack Complex. 抑制膜攻击复合物的人源化C6单克隆抗体的开发、鉴定和体内验证。

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2022-05-12 DOI: 10.1159/000524587

Heidi Gytz Olesen, Iliana Michailidou, Wioleta M Zelek, Jeroen Vreijling, Patrick Ruizendaal, Ferry de Klein, J Arnoud Marquart, Thomas B Kuipers, Hailiang Mei, Yuchun Zhang, Muhammad Ahasan, Krista K Johnson, Yi Wang, B Paul Morgan, Marcus van Dijk, Kees Fluiter, Gregers Rom Andersen, Frank Baas

{"title":"Development, Characterization, and in vivo Validation of a Humanized C6 Monoclonal Antibody that Inhibits the Membrane Attack Complex.","authors":"Heidi Gytz Olesen, Iliana Michailidou, Wioleta M Zelek, Jeroen Vreijling, Patrick Ruizendaal, Ferry de Klein, J Arnoud Marquart, Thomas B Kuipers, Hailiang Mei, Yuchun Zhang, Muhammad Ahasan, Krista K Johnson, Yi Wang, B Paul Morgan, Marcus van Dijk, Kees Fluiter, Gregers Rom Andersen, Frank Baas","doi":"10.1159/000524587","DOIUrl":"10.1159/000524587","url":null,"abstract":"Damage and disease of nerves activates the complement system. We demonstrated that activation of the terminal pathway of the complement system leads to the formation of the membrane attack complex (MAC) and delays regeneration in the peripheral nervous system. Animals deficient in the complement component C6 showed improved recovery after neuronal trauma. Thus, inhibitors of the MAC might be of therapeutic use in neurological disease. Here, we describe the development, structure, mode of action, and properties of a novel therapeutic monoclonal antibody, CP010, against C6 that prevents formation of the MAC in vivo. The monoclonal antibody is humanized and specific for C6 and binds to an epitope in the FIM1-2 domain of human and primate C6 with sub-nanomolar affinity. Using biophysical and structural studies, we show that the anti-C6 antibody prevents the interaction between C6 and C5/C5b by blocking the C6 FIM1-2:C5 C345c axis. Systemic administration of the anti-C6 mAb caused complete depletion of free C6 in circulation in transgenic rats expressing human C6 and thereby inhibited MAC formation. The antibody prevented disease in experimental autoimmune myasthenia gravis and ameliorated relapse in chronic relapsing experimental autoimmune encephalomyelitis in human C6 transgenic rats. CP010 is a promising complement C6 inhibitor that prevents MAC formation. Systemic administration of this C6 monoclonal antibody has therapeutic potential in the treatment of neuronal disease.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"1 1","pages":"16-36"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10643903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42867411","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

Bruton's Tyrosine Kinase in Neutrophils Is Crucial for Host Defense against Klebsiella pneumoniae. 中性粒细胞中的布鲁顿酪氨酸激酶对宿主防御肺炎克雷伯菌至关重要。

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2022-05-10 DOI: 10.1159/000524583

Zhe Liu, Alexander P N A De Porto, Regina De Beer, Joris J T H Roelofs, Onno J De Boer, Sandrine Florquin, Cornelis Van't Veer, Rudi W Hendriks, Tom Van der Poll, Alex F De Vos

{"title":"Bruton's Tyrosine Kinase in Neutrophils Is Crucial for Host Defense against Klebsiella pneumoniae.","authors":"Zhe Liu, Alexander P N A De Porto, Regina De Beer, Joris J T H Roelofs, Onno J De Boer, Sandrine Florquin, Cornelis Van't Veer, Rudi W Hendriks, Tom Van der Poll, Alex F De Vos","doi":"10.1159/000524583","DOIUrl":"10.1159/000524583","url":null,"abstract":"Humans with dysfunctional Bruton's tyrosine kinase (Btk) are highly susceptible to bacterial infections. Compelling evidence indicates that Btk is essential for B cell-mediated immunity, whereas its role in myeloid cell-mediated immunity against infections is controversial. In this study, we determined the contribution of Btk in B cells and neutrophils to host defense against the extracellular bacterial pathogen Klebsiella pneumoniae, a common cause of pulmonary infections and sepsis. Btk-/- mice were highly susceptible to Klebsiella infection, which was not reversed by Btk re-expression in B cells and restoration of natural antibody levels. Neutrophil-specific Btk deficiency impaired host defense against Klebsiella to a similar extent as complete Btk deficiency. Neutrophil-specific Btk deficiency abolished extracellular reactive oxygen species production in response to Klebsiella. These data indicate that expression of Btk in neutrophils is crucial, while in B cells, it is dispensable for in vivo host defense against K. pneumoniae.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"1 1","pages":"1-15"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10643901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45364696","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

The Intersection between Bacterial Metabolism and Innate Immunity. 细菌代谢和先天免疫之间的交叉点。

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-10-27 DOI: 10.1159/000534872

Ivan C Acosta, Francis Alonzo

{"title":"The Intersection between Bacterial Metabolism and Innate Immunity.","authors":"Ivan C Acosta, Francis Alonzo","doi":"10.1159/000534872","DOIUrl":"10.1159/000534872","url":null,"abstract":"Background: The innate immune system is the first line of defense against microbial pathogens and is essential for maintaining good health. If pathogens breach innate barriers, the likelihood of infection is significantly increased. Many bacterial pathogens pose a threat to human health on account of their ability to evade innate immunity and survive in growth-restricted environments. These pathogens have evolved sophisticated strategies to obtain nutrients as well as manipulate innate immune responses, resulting in disease or chronic infection.Summary: The relationship between bacterial metabolism and innate immunity is complex. Although aspects of bacterial metabolism can be beneficial to the host, particularly those related to the microbiota and barrier integrity, others can be harmful. Several bacterial pathogens harness metabolism to evade immune responses and persist during infection. The study of these adaptive traits provides insight into the roles of microbial metabolism in pathogenesis that extend beyond energy balance. This review considers recent studies on bacterial metabolic pathways that promote infection by circumventing several facets of the innate immune system. We also discuss relationships between innate immunity and antibiotics and highlight future directions for research in this field.Key messages: Pathogenic bacteria have a remarkable capacity to harness metabolism to manipulate immune responses and promote pathogenesis. While we are beginning to understand the multifaceted and complex metabolic adaptations that occur during infection, there is still much to uncover with future research.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"782-803"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71412551","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

Human Ribonuclease 6 Has a Protective Role during Experimental Urinary Tract Infection. 人核糖核酸酶6在实验性尿路感染中的保护作用

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-11-18 DOI: 10.1159/000534736

Juan de Dios Ruiz-Rosado, Hanna Cortado, Macie Kercsmar, Birong Li, Gregory Ballash, Israel Cotzomi-Ortega, Yuriko I Sanchez-Zamora, Sudipti Gupta, Christina Ching, Ester Boix, Ashley R Jackson, John David Spencer, Brian Becknell

{"title":"Human Ribonuclease 6 Has a Protective Role during Experimental Urinary Tract Infection.","authors":"Juan de Dios Ruiz-Rosado, Hanna Cortado, Macie Kercsmar, Birong Li, Gregory Ballash, Israel Cotzomi-Ortega, Yuriko I Sanchez-Zamora, Sudipti Gupta, Christina Ching, Ester Boix, Ashley R Jackson, John David Spencer, Brian Becknell","doi":"10.1159/000534736","DOIUrl":"10.1159/000534736","url":null,"abstract":"Mounting evidence suggests that antimicrobial peptides and proteins (AMPs) belonging to the RNase A superfamily have a critical role in defending the bladder and kidney from bacterial infection. RNase 6 has been identified as a potent, leukocyte-derived AMP, but its impact on urinary tract infection (UTI) in vivo has not been demonstrated. To test the functional role of human RNase 6, we generated RNASE6 transgenic mice and studied their susceptibility to experimental UTI. In addition, we generated bone marrow-derived macrophages to study the impact of RNase 6 on antimicrobial activity within a cellular context. When subjected to experimental UTI, RNASE6 transgenic mice developed reduced uropathogenic Escherichia coli (UPEC) burden, mucosal injury, and inflammation compared to non-transgenic controls. Monocytes and macrophages were the predominant cellular sources of RNase 6 during UTI, and RNASE6 transgenic macrophages were more proficient at intracellular UPEC killing than non-transgenic controls. Altogether, our findings indicate a protective role for human RNase 6 during experimental UTI.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"865-875"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10699853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138047148","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

Basic Mechanisms of Immunometabolites in Shaping the Immune Response. 免疫代谢物在形成免疫反应中的基本机制。

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-11-23 DOI: 10.1159/000535452

Dylan Gerard Ryan, Christian Graham Peace, Alexander Hooftman

{"title":"Basic Mechanisms of Immunometabolites in Shaping the Immune Response.","authors":"Dylan Gerard Ryan, Christian Graham Peace, Alexander Hooftman","doi":"10.1159/000535452","DOIUrl":"10.1159/000535452","url":null,"abstract":"Background: Innate immune cells play a crucial role in responding to microbial infections, but their improper activation can also drive inflammatory disease. For this reason, their activation state is governed by a multitude of factors, including the metabolic state of the cell and, more specifically, the individual metabolites which accumulate intracellularly and extracellularly. This relationship is bidirectional, as innate immune cell activation by pathogen-associated molecular patterns causes critical changes in cellular metabolism.Summary: In this review, we describe the emergence of various \"immunometabolites.\" We outline the general characteristics of these immunometabolites, the conditions under which they accumulate, and their subsequent impact on immune cells. We delve into well-studied metabolites of recent years, such as succinate and itaconate, as well as newly emerging immunometabolites, such as methylglyoxal.Key messages: We hope that this review may be used as a framework for further studies dissecting the mechanisms by which immunometabolites regulate the immune system and provide an outlook to harnessing these mechanisms in the treatment of inflammatory diseases.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"925-943"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10730108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138299244","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

Interleukin-33 Ameliorates Murine Systemic Lupus Erythematosus and Is Associated with Induction of M2 Macrophage Polarisation and Regulatory T Cells. 白细胞介素-33 可改善小鼠系统性红斑狼疮，并与 M2 巨噬细胞极化和调节性 T 细胞的诱导有关。

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-03-08 DOI: 10.1159/000529931

Mo Yin Mok, Ka Sin Law, Wing Yin Kong, Cai Yun Luo, Endale T Asfaw, Kwok Wah Chan, Fang Ping Huang, Chak Sing Lau, Godfrey Chi Fung Chan

{"title":"Interleukin-33 Ameliorates Murine Systemic Lupus Erythematosus and Is Associated with Induction of M2 Macrophage Polarisation and Regulatory T Cells.","authors":"Mo Yin Mok, Ka Sin Law, Wing Yin Kong, Cai Yun Luo, Endale T Asfaw, Kwok Wah Chan, Fang Ping Huang, Chak Sing Lau, Godfrey Chi Fung Chan","doi":"10.1159/000529931","DOIUrl":"10.1159/000529931","url":null,"abstract":"The innate cytokine IL-33 is increasingly recognised to possess biological effects on various immune cells. We have previously demonstrated elevated serum level of soluble ST2 in patients with active systemic lupus erythematosus suggesting involvement of IL-33 and its receptor in the lupus pathogenesis. This study sought to examine the effect of exogenous IL-33 on disease activity of pre-disease lupus-prone mice and the underlying cellular mechanisms. Recombinant IL-33 was administered to MRL/lpr mice for 6 weeks, whereas control group received phosphate-buffered saline. IL-33-treated mice displayed less proteinuria, renal histological inflammatory changes, and had lower serum levels of pro-inflammatory cytokines including IL-6 and TNF-α. Renal tissue and splenic CD11b+ extracts showed features of M2 polarisation with elevated mRNA expression of Arg1, FIZZI, and reduced iNOS. These mice also had increased IL-13, ST2, Gata3, and Foxp3 mRNA expression in renal and splenic tissues. Kidneys of these mice displayed less CD11b+ infiltration, had downregulated MCP-1, and increased infiltration of Foxp3-expressing cells. Splenic CD4+ T cells showed increased ST2-expressing CD4+Foxp3+ population and reduced IFN-γ+ population. There were no differences in serum anti-dsDNA antibodies and renal C3 and IgG2a deposit in these mice. Exogenous IL-33 was found to ameliorate disease activity in lupus-prone mice with induction of M2 polarisation, Th2 response, and expansion of regulatory T cells. IL-33 likely orchestrated autoregulation of these cells through upregulation of ST2 expression.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"485-498"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10134067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9352307","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

MicroRNA-9-1 Attenuates Influenza A Virus Replication via Targeting Tankyrase 1. MicroRNA-9-1通过靶向Tankyrase 1减弱甲型流感病毒复制。

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-08-22 DOI: 10.1159/000532063

Gayan Bamunuarachchi, Kishore Vaddadi, Xiaoyun Yang, Quanjin Dang, Zhengyu Zhu, Sankha Hewawasam, Chaoqun Huang, Yurong Liang, Yujie Guo, Lin Liu

{"title":"MicroRNA-9-1 Attenuates Influenza A Virus Replication via Targeting Tankyrase 1.","authors":"Gayan Bamunuarachchi, Kishore Vaddadi, Xiaoyun Yang, Quanjin Dang, Zhengyu Zhu, Sankha Hewawasam, Chaoqun Huang, Yurong Liang, Yujie Guo, Lin Liu","doi":"10.1159/000532063","DOIUrl":"10.1159/000532063","url":null,"abstract":"An unstable influenza genome leads to the virus resistance to antiviral drugs that target viral proteins. Thus, identification of host factors essential for virus replication may pave the way to develop novel antiviral therapies. In this study, we investigated the roles of the poly(ADP-ribose) polymerase enzyme, tankyrase 1 (TNKS1), and the endogenous small noncoding RNA, miR-9-1, in influenza A virus (IAV) infection. Increased expression of TNKS1 was observed in IAV-infected human lung epithelial cells and mouse lungs. TNKS1 knockdown by RNA interference repressed influenza viral replication. A screen using TNKS1 3'-untranslation region (3'-UTR) reporter assays and predicted microRNAs identified that miR-9-1 targeted TNKS1. Overexpression of miR-9-1 reduced influenza viral replication in lung epithelial cells as measured by viral mRNA and protein levels as well as virus production. miR-9-1 induced type I interferon production and enhanced the phosphorylation of STAT1 in cell culture. The ectopic expression of miR-9-1 in the lungs of mice by using an adenoviral viral vector enhanced type I interferon response, inhibited viral replication, and reduced susceptibility to IAV infection. Our results indicate that miR-9-1 is an anti-influenza microRNA that targets TNKS1 and enhances cellular antiviral state.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"647-664"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/85/85/jin-2023-0015-0001-532063.PMC10601686.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10048201","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

CLIPB4 Is a Central Node in the Protease Network that Regulates Humoral Immunity in Anopheles gambiae Mosquitoes. CLIPB4是调节冈比亚按蚊体液免疫的蛋白酶网络中的一个中心节点。

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-09-13 DOI: 10.1159/000533898

Xiufeng Zhang, Shasha Zhang, Junyao Kuang, Kathleen A Sellens, Bianca Morejon, Sally A Saab, Miao Li, Eve C Metto, Chunju An, Christopher T Culbertson, Mike A Osta, Caterina Scoglio, Kristin Michel

{"title":"CLIPB4 Is a Central Node in the Protease Network that Regulates Humoral Immunity in Anopheles gambiae Mosquitoes.","authors":"Xiufeng Zhang, Shasha Zhang, Junyao Kuang, Kathleen A Sellens, Bianca Morejon, Sally A Saab, Miao Li, Eve C Metto, Chunju An, Christopher T Culbertson, Mike A Osta, Caterina Scoglio, Kristin Michel","doi":"10.1159/000533898","DOIUrl":"10.1159/000533898","url":null,"abstract":"Insect humoral immune responses are regulated in part by protease cascades, whose components circulate as zymogens in the hemolymph. In mosquitoes, these cascades consist of clip-domain serine proteases (cSPs) and/or their non-catalytic homologs, which form a complex network, whose molecular make-up is not fully understood. Using a systems biology approach, based on a co-expression network of gene family members that function in melanization and co-immunoprecipitation using the serine protease inhibitor (SRPN)2, a key negative regulator of the melanization response in mosquitoes, we identify the cSP CLIPB4 from the African malaria mosquito Anopheles gambiae as a central node in this protease network. CLIPB4 is tightly co-expressed with SRPN2 and forms protein complexes with SRPN2 in the hemolymph of immune-challenged female mosquitoes. Genetic and biochemical approaches validate our network analysis and show that CLIPB4 is required for melanization and antibacterial immunity, acting as a prophenoloxidase (proPO)-activating protease, which is inhibited by SRPN2. In addition, we provide novel insight into the structural organization of the cSP network in An. gambiae, by demonstrating that CLIPB4 is able to activate proCLIPB8, a cSP upstream of the proPO-activating protease CLIPB9. These data provide the first evidence that, in mosquitoes, cSPs provide branching points in immune protease networks and deliver positive reinforcement in proPO activation cascades.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"680-696"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/42/37/jin-2023-0015-0001-533898.PMC10603620.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10228904","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

Selected β-Glucans Act as Immune-Training Agents by Improving Anti-Mycobacterial Activity in Human Macrophages: A Pilot Study. 一项初步研究表明，选定的β-葡聚糖通过提高人体巨噬细胞的抗分枝杆菌活性，起到免疫训练剂的作用。

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-09-21 DOI: 10.1159/000533873

Clara Braian, Lovisa Karlsson, Jyotirmoy Das, Maria Lerm

{"title":"Selected β-Glucans Act as Immune-Training Agents by Improving Anti-Mycobacterial Activity in Human Macrophages: A Pilot Study.","authors":"Clara Braian, Lovisa Karlsson, Jyotirmoy Das, Maria Lerm","doi":"10.1159/000533873","DOIUrl":"10.1159/000533873","url":null,"abstract":"Epigenetic reprogramming of innate immune cells by β-glucan in a process called trained immunity leads to an enhanced host response to a secondary infection. β-Glucans are structural components of plants, algae, fungi, and bacteria and thus recognized as non-self by human macrophages. We selected the β-glucan curdlan from Alcaligenes faecalis, WGP dispersible from Saccharomyces cerevisiae, and β-glucan-rich culture supernatant of Alternaria and investigated whether they could produce trained immunity effects leading to an increased control of virulent Mycobacterium tuberculosis. We observed a significant M. tuberculosis growth reduction in macrophages trained with curdlan and Alternaria, which also correlated with increased IL-6 and IL-1β release. WGP dispersible-trained macrophages were stratified into \"non-responders\" and \"responders,\" according to their ability to control M. tuberculosis, with \"responders\" producing higher IL-6 levels. The addition of neutrophils to infected macrophage cultures further enhanced macrophage control of virulent M. tuberculosis, but not in a stimuli-dependent manner. Pathway enrichment analysis of DNA methylome data also highlighted hypomethylation of genes in pathways associated with signaling and cellular reorganization and motility, and \"responders\" to WGP training were enriched in the interferon-gamma signaling pathway. This study adds evidence that certain β-glucans show promise as immune-training agents.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"751-764"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41139014","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