DOCSLIB.ORG

Aspergillosis TRIF-Dependent Immune Protection in PTX3 Binds MD-2 and Promotes

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Aspergillosis TRIF-Dependent Immune Protection in PTX3 Binds MD-2 and Promotes PTX3 Binds MD-2 and Promotes TRIF-Dependent Immune Protection in Aspergillosis This information is current as Silvia Bozza, Silvia Campo, Brunilde Arseni, Antonio of September 25, 2021. Inforzato, Lindstedt Ragnar, Barbara Bottazzi, Alberto Mantovani, Silvia Moretti, Vasileios Oikonomous, Rita De Santis, Agostinho Carvalho, Giovanni Salvatori and Luigina Romani J Immunol 2014; 193:2340-2348; Prepublished online 21 Downloaded from July 2014; doi: 10.4049/jimmunol.1400814 http://www.jimmunol.org/content/193/5/2340 http://www.jimmunol.org/ Supplementary http://www.jimmunol.org/content/suppl/2014/07/18/jimmunol.140081 Material 4.DCSupplemental References This article cites 41 articles, 15 of which you can access for free at: http://www.jimmunol.org/content/193/5/2340.full#ref-list-1 Why The JI? Submit online. by guest on September 25, 2021 • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2014 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology PTX3 Binds MD-2 and Promotes TRIF-Dependent Immune Protection in Aspergillosis Silvia Bozza,* Silvia Campo,† Brunilde Arseni,† Antonio Inforzato,† Lindstedt Ragnar,† Barbara Bottazzi,‡ Alberto Mantovani,‡ Silvia Moretti,* Vasileios Oikonomous,* Rita De Santis,† Agostinho Carvalho,* Giovanni Salvatori,† and Luigina Romani* The long pentraxin 3 (PTX3) modulates different effector pathways involved in innate resistance to Aspergillus fumigatus, including complement activation or promotion of phagocytosis by interacting with FcgRs. However, whether and how TLRs modulate PTX3 mediates antifungal resistance is not known. In this study, we demonstrate that PTX3 binds myeloid differentiation protein 2 (MD-2) in vitro and exerts its protective antifungal activity in vivo through TLR4/MD-2–mediated signaling. Similar to Tlr42/2 mice, Md22/2 mice displayed high susceptibility to pulmonary aspergillosis, a phenotype associated with a proinflammatory cytokine profile and impaired antifungal activity of polymorphonuclear neutrophils. Treating Md22/2 mice with PTX3 failed to Downloaded from confer immune protection against the fungus, whereas adoptive transfer of MD-2–competent polymorphonuclear neutrophils restored it. Mechanistically, engagement of MD-2 by PTX3-opsonized Aspergillus conidia activated the TLR4/Toll/IL-1R domain-containing adapter inducing IFN-b–dependent signaling pathway converging on IL-10. Thus, we have identified a novel receptor mechanism, involving the TLR4/MD-2/Toll/IL-1R domain-containing adapter inducing IFN-b–mediated signaling, whereby PTX3 elicits antifun- gal resistance with limited immunopathology in A. fumigatus infection. The Journal of Immunology, 2014, 193: 2340–2348. http://www.jimmunol.org/ nvasive aspergillosis is an infection caused by fungi of the pulmonary aspergillosis in immunocompetent individuals (8). genus Aspergillus that typically affects severely immuno- TLR4 signaling in response to its prototype ligand LPS relies on I compromised hematologic patients undergoing intensive che- the action of two accessory molecules, myeloid differentiation motherapy and bone marrow or solid organ transplantation (1–3). protein 2 (MD-2) (9) and CD14 (10), which are essential for the Despite the availability of new azole and echinochandin drugs that stabilization of TLR4 expression on the cell surface following have significantly improved the management of this severe infection, activation by LPS (11, 12). As a matter of fact, TLR4 is unable to the prevention, diagnosis, and therapy of aspergillosis remain ex- induce a complete response to LPS in the absence of MD-2 (9), tremely difficult, rendering it a leading cause of death among im- a glycoprotein that belongs to the MD-2–related lipid recognition by guest on September 25, 2021 munocompromised patients, with a 1-y mortality reaching 75% (1). family (13), that is a critical compound in host response to Gram- The immune response to Aspergillus fumigatus is critically de- negative bacteria and plays a central role in physiologic adaptation pendent on the recognition of fungal motifs, mostly cell wall com- to various insults (14). ponents, by pattern recognition receptors (4). TLR4 has been Of interest, naturally occurring alternatively spliced isoforms of demonstrated as one major pattern recognition receptor required for human MD-2 acted as a negative regulator of LPS-mediated TLR4 resistance to A. fumigatus infection (5). Consistently, a missense activation (15), a finding indicating that targeting MD-2 could mutation affecting the extracellular domain of human TLR4 was inhibit TLR4 inflammatory signaling, as recently suggested (16). found to be associated with increased susceptibility to Aspergillus Due to the conserved nature of the TLR4/MD-2/CD14 complex, pneumonia (6) and colonization (7) in recipients of allogeneic he- several reports have suggested that it is biologically relevant and matopoietic stem cell transplants, as well as to chronic cavitary responsive to several microorganisms, including bacteria (17, 18) and viruses (19). However, little is known about whether and how the TLR4/MD-2/CD14 complex mediates immune responses to *Department of Experimental Medicine, University of Perugia, Perugia 06132, Italy; †Department of Immunology, Sigma-Tau S.p.A., Pomezia 00040, Italy; and A. fumigatus. ‡Istituto Clinico Humanitas, Rozzano, Milan 20089, Italy Fungal sensing is assisted by the action of several molecules, Received for publication March 31, 2014. Accepted for publication June 19, 2014. including collectins, ficolins, pentraxins, and complement compo- This work was supported by Italian Projects PRIN 2009HL28E8_002 (to S.B.), nents that act as opsonins and facilitate the interaction of phagocytes Research Grant RS_R_280100 from Sigma-Tau (to L.R.), and European Commu- with fungi (20). Among these, the long pentraxin 3 (PTX3) has been nity Grant ERC-2011-AdG-293714 (to L.R.). found to have a nonredundant protective role in the immune re- Address correspondence and reprint requests to Prof. Luigina Romani, Department of Experimental Medicine, University of Perugia, Piazzale Gambuli, Polo Unico sponse to A. fumigatus (21). PTX3 modulates different effector Sant’Andrea delle Fratte, Perugia 06132, Italy. E-mail address: luigina. pathways involved in innate resistance to A. fumigatus, including [email protected] complement activation, promotion of phagocytosis, and regulation The online version of this article contains supplemental material. of inflammation (22–26). The molecular mechanisms underlying Abbreviations used in this article: BAL, bronchoalveolar lavage; DC, dendritic cell; the opsonic activity of PTX3 and increased phagocytosis of conidia HSCT, hematopoietic stem cell transplantation; IKK, IkB kinase; i.n., intranasal; IRF3, IFN regulatory factor 3; MD-2, myeloid differentiation protein 2; PAS, peri- by neutrophils involved FcgRII-, CD11b-, and complement- odic acid-Schiff; PMN, polymorphonuclear neutrophil; PTX3, pentraxin 3; sMD-2, dependent mechanisms (26). However, the PTX3 protective ac- soluble MD-2; TLN, thoracic lymph node; Treg, regulatory T; TRIF, Toll/IL-1R tivity against CMV was impaired in TLR4-deficient mice (27), domain-containing adapter inducing IFN-b; WT, wild-type. a finding suggesting some level of cooperation between TLR4 and Copyright Ó 2014 by The American Association of Immunologists, Inc. 0022-1767/14/$16.00 PTX3 in host antimicrobial immunity. www.jimmunol.org/cgi/doi/10.4049/jimmunol.1400814 The Journal of Immunology 2341 In the current study, we sought to investigate the contribution of Collection of bronchoalveolar lavage fluid the TLR4/MD-2/CD14 complex to the PTX3-dependent activity Lungs were filled thoroughly with 1-ml aliquots of pyrogen-free saline through against A. fumigatus. Our findings demonstrate that PTX3 activates a 22-gauge bead-tipped feeding needle introduced into the trachea. Bron- the TLR4/Toll/IL-1R domain-containing adapter inducing IFN-b choalveolar lavage (BAL) fluid was collected in a plastic tube on ice and (TRIF)–dependent signaling pathway converging on IDO and IL-10 centrifuged at 400 3 g at 4˚C for 5 min. For differential BAL fluid cell counts, € upon binding MD-2. cytospin preparations were made and stained with May-Grunwald Giemsa reagents (Sigma-Aldrich). At least 200 cells/field/10 fields were counted, and the absolute number of each cell type was calculated (25). Photographs were taken using a using a BX51 microscope (Olympus, Milan, Italy), and images Materials and Methods were captured using a high-resolution DP71 camera (Olympus). Binding assays Treatment HEK293TCM, HEK293CM, and HEK293T cells expressing human TLR4A/ MD-2/CD14 or TLR4A and CD14/MD-2 (Invivogen), respectively, were Human PTX3 was obtained under endotoxin-free conditions by immu- used. The control line was HEK293Null. Binding of PTX3 to HEK293 noaffinity
Load more

Recommended publications
  • Pentraxin-2 Suppresses C-Jun/AP-1 Signaling to Inhibit Progressive Fibrotic Disease
    Pentraxin-2 suppresses c-Jun/AP-1 signaling to inhibit progressive fibrotic disease Naoki Nakagawa, … , Sina A. Gharib, Jeremy S. Duffield JCI Insight. 2016;1(20):e87446. https://doi.org/10.1172/jci.insight.87446. Research Article Immunology Inflammation Pentraxin-2 (PTX-2), also known as serum amyloid P component (SAP/APCS), is a constitutive, antiinflammatory, innate immune plasma protein whose circulating level is decreased in chronic human fibrotic diseases. Here we show that recombinant human PTX-2 (rhPTX-2) retards progression of chronic kidney disease in Col4a3 mutant mice with Alport syndrome, reducing blood markers of kidney failure, enhancing lifespan by 20%, and improving histological signs of disease. Exogenously delivered rhPTX-2 was detected in macrophages but also in tubular epithelial cells, where it counteracted macrophage activation and was cytoprotective for the epithelium. Computational analysis of genes regulated by rhPTX-2 identified the transcriptional regulator c-Jun along with its activator protein–1 (AP-1) binding partners as a central target for the function of rhPTX-2. Accordingly, PTX-2 attenuates c-Jun and AP-1 activity, and reduces expression of AP-1–dependent inflammatory genes in both monocytes and epithelium. Our studies therefore identify rhPTX-2 as a potential therapy for chronic fibrotic disease of the kidney and an important inhibitor of pathological c-Jun signaling in this setting. Find the latest version: https://jci.me/87446/pdf RESEARCH ARTICLE Pentraxin-2 suppresses c-Jun/AP-1 signaling to inhibit progressive fibrotic disease Naoki Nakagawa,1,2,3 Luke Barron,4 Ivan G. Gomez,1,2,4 Bryce G.
    [Show full text]
  • Pentraxin-3 to Better Delineate Necrotizing Soft Tissue Infection: Not Really! Patrick M
    Honore and Spapen Critical Care (2016) 20:173 DOI 10.1186/s13054-016-1319-0 LETTER Open Access Pentraxin-3 to better delineate necrotizing soft tissue infection: not really! Patrick M. Honore* and Herbert D. Spapen See related research by Hansen et al., http://ccforum.biomedcentral.com/articles/10.1186/s13054-016-1210-z Necrotizing soft tissue infection (NSTI) is a devastating assessment and persistently elevated levels during evolv- condition with high morbidity and a dismal prognosis. ing sepsis may contribute to tissue damage and predict Timely and adequate surgery and early aggressive treat- poor patient outcome [2]. Second, when looking closely ment of associated sepsis are imperative to improve at the study results, PTX3 levels appeared to be fairly in survival [1–3]. Pentraxin-3 (PTX3) is a glycoprotein line with PCT concentrations for assessing NSTI- released by endothelial and inflammatory cells upon associated morbidity and mortality. PCT also outper- stimulation by cytokines and endotoxins. In contrast with forms CRP in predicting severity of infection and organ C-reactive protein (CRP) which is produced in the liver in dysfunction in sepsis [4] but is more readily available response to systemic inflammation, PTX3 is thought to than PTX3. Finally, many patients with NSTI develop better reflect local vascular inflammation and bacterial acute kidney injury, necessitating renal replacement load [2]. PTX3 assessment might thus be a more appropri- therapy (RRT) (25 % of the patients studied by Hansen ate marker of severity and prognosis of NSTI. This was et al.!). PTX3 has a molecular weight of approximately corroborated by Hansen et al.
    [Show full text]
  • Human Lectins, Their Carbohydrate Affinities and Where to Find Them
    biomolecules Review Human Lectins, Their Carbohydrate Affinities and Where to Review HumanFind Them Lectins, Their Carbohydrate Affinities and Where to FindCláudia ThemD. Raposo 1,*, André B. Canelas 2 and M. Teresa Barros 1 1, 2 1 Cláudia D. Raposo * , Andr1 é LAQVB. Canelas‐Requimte,and Department M. Teresa of Chemistry, Barros NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829‐516 Caparica, Portugal; [email protected] 12 GlanbiaLAQV-Requimte,‐AgriChemWhey, Department Lisheen of Chemistry, Mine, Killoran, NOVA Moyne, School E41 of ScienceR622 Co. and Tipperary, Technology, Ireland; canelas‐ [email protected] NOVA de Lisboa, 2829-516 Caparica, Portugal; [email protected] 2* Correspondence:Glanbia-AgriChemWhey, [email protected]; Lisheen Mine, Tel.: Killoran, +351‐212948550 Moyne, E41 R622 Tipperary, Ireland; [email protected] * Correspondence: [email protected]; Tel.: +351-212948550 Abstract: Lectins are a class of proteins responsible for several biological roles such as cell‐cell in‐ Abstract:teractions,Lectins signaling are pathways, a class of and proteins several responsible innate immune for several responses biological against roles pathogens. such as Since cell-cell lec‐ interactions,tins are able signalingto bind to pathways, carbohydrates, and several they can innate be a immuneviable target responses for targeted against drug pathogens. delivery Since sys‐ lectinstems. In are fact, able several to bind lectins to carbohydrates, were approved they by canFood be and a viable Drug targetAdministration for targeted for drugthat purpose. delivery systems.Information In fact, about several specific lectins carbohydrate were approved recognition by Food by andlectin Drug receptors Administration was gathered for that herein, purpose. plus Informationthe specific organs about specific where those carbohydrate lectins can recognition be found by within lectin the receptors human was body.
    [Show full text]
  • The Role of Triggering Receptor Expressed on Myeloid Cells-2 in Inflammation
    The role of triggering receptor expressed on myeloid cells-2 in inflammation Doctoral Thesis at the Medical University of Vienna for obtaining the academic degree Doctor of Philosophy (PhD) submitted by Maga. Riem Gawish Supervisor: Univ. Prof. Dr. Sylvia Knapp, PhD Laboratory of Infection Biology, Dept. of Medicine 1, Medical University Vienna Center for Molecular Medicine of the Austrian Academy of Sciences Währinger Gürtel 18-20, 1090 Vienna, Austria Vienna, 03/2015 The role of triggering receptor expressed on myeloid cells-2 in inflammation Riem Gawish Table of contents Declaration ................................................................................................................................. 5 List of Figures ............................................................................................................................ 6 List of tables ............................................................................................................................... 8 Abstract ...................................................................................................................................... 9 Kurzfassung ................................................................................................................................ 9 Publications arising from this thesis ......................................................................................... 12 Abbreviations (alphabetically ordered) .................................................................................... 13
    [Show full text]
  • Integrated Bioinformatics Approach to Understand Immune-Related Key
    Integrated bioinformatics approach to understand immune-related key genes and pathways in chronic spontaneous urticaria wenxing su Second Aliated Hospital of Soochow University biao huang First Aliated Hospital of Soochow University ying zhao Second Aliated Hospital of Soochow University xiaoyan zhang Second Aliated Hospital of Soochow University lu chen second aliated hospital of soochow university jiang ji ( [email protected] ) Second Aliated Hospital of Soochow University qingqing Jiao rst aliated hospital of soochow university Research Keywords: Chronic spontaneous urticaria, bioinformatical analysis, differentially expressed genes, immune inltration Posted Date: December 31st, 2020 DOI: https://doi.org/10.21203/rs.3.rs-137346/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/29 Abstract Background Chronic spontaneous urticaria (CSU) refers to recurrent urticaria that lasts for more than 6 weeks in the absence of an identiable trigger. Due to its recurrent wheal and severe itching, CSU seriously affects patients' life quality. There is currently no radical cure for it and its vague pathogenesis limits the development of targeted therapy. With the goal of revealing the underlying mechanism, two data sets with accession numbers GSE57178 and GSE72540 were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the differentially expressed genes (DEGs) of CSU skin lesion samples and healthy controls, four kinds of analyses were performed, namely functional annotation, protein- protein interaction (PPI) network and module construction, co-expression and drug-gene interaction prediction analysis, and immune and stromal cells deconvolution analyses. Results 92 up-regulated genes and 7 down-regulated genes were selected for subsequent analyses.
    [Show full text]
  • Macrophage Expression and Prognostic Significance of the Long Pentraxin PTX3 in COVID-19
    medRxiv preprint doi: https://doi.org/10.1101/2020.06.26.20139923; this version posted June 29, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. MACROPHAGE EXPRESSION AND PROGNOSTIC SIGNIFICANCE OF THE LONG PENTRAXIN PTX3 IN COVID-19 Enrico Brunetta1,2*, Marco Folci1,2*, Barbara Bottazzi1*, Maria De Santis1, Alessandro Protti1,2, Sarah Mapelli1, Roberto Leone1, Ilaria My1,2, Monica Bacci1, Veronica Zanon1, Gianmarco Spata1, Andrea Gianatti3, Marina Sironi1, Claudio Angelini1, Cecilia Garlanda1,2§, Michele Ciccarelli1§, Maurizio Cecconi1,2§, Alberto Mantovani1,2,4§. *equal contributors §corresponding authors 1 Humanitas Clinical and Research Center – IRCCS, via Manzoni 56, 20089 Rozzano (Milan), Italy; 2 Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele (Milan), Italy; 3 Department of Laboratory Medicine, Anatomic Pathology, Azienda Ospedaliera ASST Papa Giovanni XXIII, Bergamo, Italy. 4 The William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ. Support This work was partially supported by the Dolce & Gabbana fashion house and by Italian Ministry of Health. Acknowledgements We are grateful to Prof. Alessandro Rambaldi and Dr. Giovanni Gritti (Azienda Ospedaliera ASST Papa Giovanni XXIII, Bergamo, Italy) for helpful discussion. We also acknowledge the work and contribution of Monica Rimoldi, Paolo Tentorio and Sonia Valentino (Humanitas Clinical and Research Center, Rozzano, Milano, Italy) for their tireless work on the collection of biological samples from COVID-19 patients. NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
    [Show full text]
  • Complement in Tumourigenesis and the Response to Cancer Therapy
    cancers Review Complement in Tumourigenesis and the Response to Cancer Therapy Rebecca M. O’Brien 1,2, Aoife Cannon 1, John V. Reynolds 1, Joanne Lysaght 1,2 and Niamh Lynam-Lennon 1,* 1 Department of Surgery, Trinity St. James’s Cancer Institute, Trinity Translational Medicine Institute, Trinity College Dublin and St. James’s Hospital, Dublin 8, Ireland; [email protected] (R.M.O.); [email protected] (A.C.); [email protected] (J.V.R.); [email protected] (J.L.) 2 Cancer Immunology and Immunotherapy Group, Trinity St. James’s Cancer Institute, Trinity Translational Medicine Institute, Trinity College Dublin and St. James’s Hospital, Dublin 8, Ireland * Correspondence: [email protected] Simple Summary: Increasing evidence supports a role for complement in the development of cancer and the response to cancer treatments. Dysregulated complement expression within the tumour microenvironment has been linked to the suppression of anti-tumour immunity and poor clinical outcomes. Complement signals have been demonstrated to alter the immune milieu, promote proliferation and facilitate metastasis. Targeting complement signalling in combination with current treatments may have the potential to achieve improved control of tumour growth. Abstract: In recent years, our knowledge of the complement system beyond innate immunity has progressed significantly. A modern understanding is that the complement system has a multifaceted role in malignancy, impacting carcinogenesis, the acquisition of a metastatic phenotype and response to therapies. The ability of local immune cells to produce and respond to complement components has provided valuable insights into their regulation, and the subsequent remodeling of the tumour Citation: O’Brien, R.M.; Cannon, A.; Reynolds, J.V.; Lysaght, J.; microenvironment.
    [Show full text]
  • Siluprot PTX3, Pentraxin-Related Protein, Human
    SILuProt PTX3, Pentraxin-related protein, human recombinant, expressed in HEK cells SIL MS Protein Standard, 13C- and 15N-labeled Catalog Number MSST0003 Storage Temperature –20 C Synonyms: Tumor necrosis factor alpha-induced Each vial contains 10–13 g of SILuProt PTX3 protein 5 (TNF alpha-induced protein 5), Tumor standard, lyophilized from a solution of phosphate necrosis factor-inducible gene 14 protein, (TSG-14) buffered saline. Vial content was determined by the Bradford method using BSA as a calibrator. The Product Description correction factor from the Bradford method to Amino SILuProt PTX3 is a recombinant, stable isotope- Acid Analysis is 110% for this protein. labeled human PTX3 which incorporates 13 15 13 15 [ C6, N4]-Arginine and [ C6, N2]-Lysine. Expressed Identity: Confirmed by peptide mapping in human 293 cells, it is designed to be used as an internal standard for bioanalysis of PTX3 in mass Purity: 95% (SDS-PAGE) spectrometry. SILuProt PTX3 is a recombinant glycosylated human protein expressed in human 293 Heavy amino acid incorporation efficiency: 98% (MS) cells. It is a homooctamer and a homodecamer consisting of 364 amino acids (monomer) with a UniProt: P26022 calculated molecular mass of 40.4 kDa. It contains no tags. Sequence Information ENSDDYDLMYVNLDNEIDNGLHPTEDPTPCACGQEH Pentraxin 3 (PTX3) is a secreted glycosylated protein SEWDKLFIMLENSQMRERMLLQATDDVLRGELQRLR belonging to the pentraxin superfamily.1 PTX3 is rapidly EELGRLAESLARPCAPGAPAEARLTSALDELLQATRD produced and released by several cell types, in AGRRLARMEGAEAQRPEEAGRALAAVLEELRQTRAD
    [Show full text]
  • Pentraxin PTX3 Against Influenza Viruses Antiviral Activity of the Long Chain
    Antiviral Activity of the Long Chain Pentraxin PTX3 against Influenza Viruses Patrick C. Reading, Silvia Bozza, Brad Gilbertson, Michelle Tate, Silvia Moretti, Emma R. Job, Erika C. Crouch, Andrew This information is current as G. Brooks, Lorena E. Brown, Barbara Bottazzi, Luigina of September 26, 2021. Romani and Alberto Mantovani J Immunol 2008; 180:3391-3398; ; doi: 10.4049/jimmunol.180.5.3391 http://www.jimmunol.org/content/180/5/3391 Downloaded from References This article cites 45 articles, 16 of which you can access for free at: http://www.jimmunol.org/content/180/5/3391.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 26, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2008 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Antiviral Activity of the Long Chain Pentraxin PTX3 against Influenza Viruses1 Patrick C. Reading,2* Silvia Bozza,† Brad Gilbertson,* Michelle Tate,* Silvia Moretti,† Emma R.
    [Show full text]
  • Diagnostic Value of Pentraxin-3 in Patients with Sepsis and Septic Shock in Accordance with Latest Sepsis-3 Definitions
    Hamed et al. BMC Infectious Diseases (2017) 17:554 DOI 10.1186/s12879-017-2606-3 RESEARCHARTICLE Open Access Diagnostic value of Pentraxin-3 in patients with sepsis and septic shock in accordance with latest sepsis-3 definitions Sonja Hamed1†, Michael Behnes1*† , Dominic Pauly1, Dominic Lepiorz1, Max Barre1, Tobias Becher1, Siegfried Lang1, Ibrahim Akin1, Martin Borggrefe1, Thomas Bertsch2 and Ursula Hoffmann1 Abstract Background: Pentraxin-3 (PTX-3) is an acute-phase protein involved in inflammatory and infectious processes. This study assesses its diagnostic and prognostic value in patients with sepsis or septic shock in a medical intensive care unit (ICU). Methods: The study includes 213 ICU patients with clinical criteria of sepsis and septic shock. 77 donors served as controls. Plasma levels of PTX-3, procalcitonin (PCT) and interleukin-6 were measured on day 1, 3 and 8. Results: PTX-3 correlated with higher lactate levels as well as with APACHE II and SOFA scores (p = 0.0001). PTX-3 levels of patients with sepsis or septic shock were consistently significantly higher than in the control group (p ≤ 0.001). Plasma levels were able to discriminate sepsis and septic shock significantly on day 1, 3 and 8 (range of AUC 0.73–0.92, p = 0.0001). Uniform cut-off levels were defined at ≥5 ng/ml for at least sepsis, ≥9ng/mlforsepticshock(p = 0.0001). Conclusion: PTX-3revealsdiagnosticvalueforsepsisandsepticshockduringthefirstweekofintensivecaretreatment, comparable to interleukin-6 according to latest Sepsis-3 definitions. Trial registration: NCT01535534. Registered 14.02.2012 Keywords: Sepsis, Septic shock, Pentraxin-3, ICU, Biomarkers, Sepsis-3 Background unacceptably high despite the developments of modern Sepsis is a widely common clinical syndrome, caused by intensive care medicine.
    [Show full text]
  • Pseudomonas Aeruginosa Dnak Stimulates the Production of Pentraxin 3 Via TLR4-Dependent NF-B and ERK Signaling Pathways
    International Journal of Molecular Sciences Article Pseudomonas aeruginosa DnaK Stimulates the Production of Pentraxin 3 via TLR4-Dependent NF-κB and ERK Signaling Pathways Jisu Jeon 1, Yeji Lee 1, Hyeonseung Yu 1,2 and Unhwan Ha 1,2,* 1 Department of Biotechnology and Bioinformatics, Korea University, Sejong 30019, Korea; [email protected] (J.J.); [email protected] (Y.L.); [email protected] (H.Y.) 2 Interdisciplinary Graduate Program for Artificial Intelligence Smart Convergence Technology, Korea University, Sejong 30019, Korea * Correspondence: [email protected]; Tel.: +82-44-860-1418; Fax: +82-44-860-1598 Abstract: Microbe-derived factors trigger innate immune responses through the production of in- flammatory mediators, including pentraxin 3 (PTX3). PTX3 is a soluble pattern recognition molecule that stimulates the clearance of clinically important bacterial pathogens such as Pseudomonas aerug- inosa. However, the P. aeruginosa factors responsible for the production of PTX3 have not been elucidated. In this study, we found that P. aeruginosa DnaK, a homolog of heat shock protein 70, induced PTX3 production. Induction was mediated by intracellular signals transmitted through the Toll-like receptor 4 (TLR4) signaling pathway. Following receptor engagement, the stimulatory signals were relayed initially through the nuclear factor kappa B (NF-κB) signaling pathway and subsequently by extracellular signal-regulated kinases (ERK), which are mitogen-activated protein kinases. However, ERK activation was negatively controlled by NF-κB, implying the existence of neg- ative crosstalk between the NF-κB and the ERK pathways. These data suggest that P. aeruginosa DnaK Citation: Jeon, J.; Lee, Y.; Yu, H.; Ha, acts as a pathogen-associated molecular pattern to trigger modulation of host defense responses via U.
    [Show full text]
  • Pentraxin 3 Deficiency Exacerbates Lipopolysaccharide-Induced Inflammation in Adipose Tissue
    International Journal of Obesity (2020) 44:525–538 https://doi.org/10.1038/s41366-019-0402-4 ARTICLE Adipocyte and Cell Biology Pentraxin 3 deficiency exacerbates lipopolysaccharide-induced inflammation in adipose tissue 1 1 1 1 1 Hong Guo ● Xiaoxue Qiu ● Jessica Deis ● Te-Yueh Lin ● Xiaoli Chen Received: 15 January 2019 / Revised: 12 April 2019 / Accepted: 27 April 2019 / Published online: 17 June 2019 © The Author(s), under exclusive licence to Springer Nature Limited 2019 Abstract Background/objectives Pentraxin 3 (PTX3) has been characterized as a soluble and multifunctional pattern recognition protein in the regulation of innate immune response. However, little is known about its role in adipose tissue inflammation and obesity. Herein, we investigated the role of PTX3 in the regulation of lipopolysaccharide (LPS)-induced inflammation in adipocytes and adipose tissue, as well as high-fat diet (HFD)-induced metabolic inflammation in obesity. Methods Ptx3 knockdown 3T3-L1 Cells were generated using shRNA for Ptx3 gene and treated with different inflammatory stimuli. For the in vivo studies, Ptx3 knockout mice were treated with 0.3 mg/kg of LPS for 6 h. Adipose tissues were collected for gene and protein expression by qPCR and western blotting, respectively. Ptx3 knockout mice were fed with 1234567890();,: 1234567890();,: HFD for 12 week since 6 week of age. Results We observed that the expression of PTX3 in adipose tissue and serum PTX3 were markedly increased in response to LPS administration. Knocking down Ptx3 in 3T3-L1 cells reduced adipogenesis and caused a more profound and sustained upregulation of proinflammatory gene expression and signaling pathway activation during LPS-stimulated inflammation in 3T3-L1 adipocytes.
    [Show full text]