A System Dynamics Model to Predict the Human Monocyte Response to Endotoxins.

Abstract:

:System dynamics is a powerful tool that allows modeling of complex and highly networked systems such as those found in the human immune system. We have developed a model that reproduces how the exposure of human monocytes to lipopolysaccharides (LPSs) induces an inflammatory state characterized by high production of tumor necrosis factor alpha (TNFα), which is rapidly modulated to enter into a tolerant state, known as endotoxin tolerance (ET). The model contains two subsystems with a total of six states, seven flows, two auxiliary variables, and 14 parameters that interact through six differential and nine algebraic equations. The parameters were estimated and optimized to obtain a model that fits the experimental data obtained from human monocytes treated with various LPS doses. In contrast to publications on other animal models, stimulation of human monocytes with super-low-dose LPSs did not alter the response to a second LPSs challenge, neither inducing ET, nor enhancing the inflammatory response. Moreover, the model confirms the low production of TNFα and increased levels of C-C motif ligand 2 when monocytes exhibit a tolerant state similar to that of patients with sepsis. At present, the model can help us better understand the ET response and might offer new insights on sepsis diagnostics and prognosis by examining the monocyte response to endotoxins in patients with sepsis.

journal_name

Front Immunol

journal_title

Frontiers in immunology

authors

Álvarez E,Toledano V,Morilla F,Hernández-Jiménez E,Cubillos-Zapata C,Varela-Serrano A,Casas-Martín J,Avendaño-Ortiz J,Aguirre LA,Arnalich F,Maroun-Eid C,Martín-Quirós A,Quintana Díaz M,López-Collazo E

doi

10.3389/fimmu.2017.00915

subject

Has Abstract

pub_date

2017-08-03 00:00:00

pages

915

issn

1664-3224

journal_volume

8

pub_type

杂志文章
  • Cecal CircRNAs Are Associated With the Response to Salmonella Enterica Serovar Enteritidis Inoculation in the Chicken.

    abstract::Circular RNAs (circRNAs) are a class of endogenous noncoding RNA, which is different from linear RNA. CircRNA is an RNA molecule with a closed loop structure formed by reverse splicing. CircRNAs have been studied in several organisms, however, the circRNAs associated with the response to Salmonella enterica serovar En...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.01186

    authors: Zheng L,Liu L,Lin L,Tang H,Fan X,Lin H,Li X

    更新日期:2019-05-31 00:00:00

  • Emerging Concepts about NAIP/NLRC4 Inflammasomes.

    abstract::Neuronal apoptosis inhibitory protein (NAIP)/NOD-like receptor (NLR) containing a caspase activating and recruitment domain (CARD) 4 (NLRC4) inflammasome complexes are activated in response to proteins from virulent bacteria that reach the cell cytosol. Specific NAIP proteins bind to the agonists and then physically a...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2014.00309

    authors: Lage SL,Longo C,Branco LM,da Costa TB,Buzzo Cde L,Bortoluci KR

    更新日期:2014-07-02 00:00:00

  • Anti-Interleukin-6 Promotes Allogeneic Bone Marrow Engraftment and Prolonged Graft Survival in an Irradiation-Free Murine Transplant Model.

    abstract::Transfer of recipient regulatory T cells (Tregs) induces mixed chimerism and tolerance in an irradiation-free bone marrow (BM) transplantation (BMT) model involving short-course co-stimulation blockade and mTOR inhibition. Boosting endogenous Tregs pharmacologically in vivo would be an attractive alternative avoiding ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00821

    authors: Granofszky N,Farkas AM,Muckenhuber M,Mahr B,Unger L,Maschke S,Pilat N,Holly R,Wiletel M,Regele H,Wekerle T

    更新日期:2017-07-19 00:00:00

  • Effect of Roux-en-Y Bariatric Surgery on Lipoproteins, Insulin Resistance, and Systemic and Vascular Inflammation in Obesity and Diabetes.

    abstract:Purpose:Obesity is a major modifiable risk factor for cardiovascular disease. Bariatric surgery is considered to be the most effective treatment option for weight reduction in obese patients with and without type 2 diabetes (T2DM). Objective:To evaluate changes in lipoproteins, insulin resistance, mediators of systemi...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01512

    authors: Yadav R,Hama S,Liu Y,Siahmansur T,Schofield J,Syed AA,France M,Pemberton P,Adam S,Ho JH,Aghamohammadzadeh R,Dhage S,Donn R,Malik RA,New JP,Jeziorska M,Durrington P,Ammori BA,Soran H

    更新日期:2017-11-15 00:00:00

  • The critical role of the tumor microenvironment in shaping natural killer cell-mediated anti-tumor immunity.

    abstract::Considerable evidence has been gathered over the last 10 years showing that the tumor microenvironment (TME) is not simply a passive recipient of immune cells, but an active participant in the establishment of immunosuppressive conditions. It is now well documented that hypoxia, within the TME, affects the functions o...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2013.00490

    authors: Baginska J,Viry E,Paggetti J,Medves S,Berchem G,Moussay E,Janji B

    更新日期:2013-12-25 00:00:00

  • Immune Evasion Strategies of Trypanosoma brucei within the Mammalian Host: Progression to Pathogenicity.

    abstract::The diseases caused by African trypanosomes (AT) are of both medical and veterinary importance and have adversely influenced the economic development of sub-Saharan Africa. Moreover, so far not a single field applicable vaccine exists, and chemotherapy is the only strategy available to treat the disease. These strictl...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2016.00233

    authors: Stijlemans B,Caljon G,Van Den Abbeele J,Van Ginderachter JA,Magez S,De Trez C

    更新日期:2016-06-24 00:00:00

  • Role of Regulatory Immune Cells and Molecules in Autoimmune Bullous Dermatoses.

    abstract::Autoimmune bullous dermatoses (AIBD) include a series of typical organ-specific autoimmune diseases characterized by extensive mucocutaneous blisters. It is generally accepted to be caused by pathological autoantibodies that directly target specific adhesion components of the skin or the adjacent mucous membranes. Bot...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.01746

    authors: Cao T,Shao S,Fang H,Li B,Wang G

    更新日期:2019-08-02 00:00:00

  • Toll-like Interleukin 1 Receptor Regulator Is an Important Modulator of Inflammation Responsive Genes.

    abstract::TILRR (Toll-like interleukin-1 receptor regulator), a transcript variant of FREM1, is a novel regulatory component, which stimulates innate immune responses through binding to IL-1R1 (Interleukin-1 receptor, type 1) and TLR (Toll-like receptor) complex. However, it is not known whether TILRR expression influences othe...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00272

    authors: Kashem MA,Li H,Toledo NP,Omange RW,Liang B,Liu LR,Li L,Yang X,Yuan XY,Kindrachuk J,Plummer FA,Luo M

    更新日期:2019-02-28 00:00:00

  • Mycobacterium bovis Bacillus Calmette-Guérin Alters Melanoma Microenvironment Favoring Antitumor T Cell Responses and Improving M2 Macrophage Function.

    abstract::Intralesional Mycobacterium bovis bacillus Calmette-Guérin (BCG) has long been a relatively inexpensive therapy for inoperable cutaneous metastatic melanoma (CMM), although intralesional BCG skin mechanisms remain understudied. We analyzed intralesional BCG-treated CMM lesions combined with in vitro studies to further...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00965

    authors: Lardone RD,Chan AA,Lee AF,Foshag LJ,Faries MB,Sieling PA,Lee DJ

    更新日期:2017-08-11 00:00:00

  • MMP-9/Gelatinase B Degrades Immune Complexes in Systemic Lupus Erythematosus.

    abstract::Systemic Lupus Erythematosus (SLE) is a common and devastating autoimmune disease, characterized by a dysregulated adaptive immune response against intracellular antigens, which involves both autoreactive T and B cells. In SLE, mainly intracellular autoantigens generate autoantibodies and these assemble into immune co...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00538

    authors: Ugarte-Berzal E,Boon L,Martens E,Rybakin V,Blockmans D,Vandooren J,Proost P,Opdenakker G

    更新日期:2019-03-22 00:00:00

  • Induction of Mycobacterium Tuberculosis Lipid-Specific T Cell Responses by Pulmonary Delivery of Mycolic Acid-Loaded Polymeric Micellar Nanocarriers.

    abstract::Mycolic acid (MA), a major lipid component of Mycobacterium tuberculosis (Mtb) cell wall, can be presented by the non-polymorphic antigen presenting molecule CD1b to T cells isolated from Mtb-infected individuals. These MA-specific CD1b-restricted T cells are cytotoxic, produce Th1 cytokines, and form memory populatio...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.02709

    authors: Shang S,Kats D,Cao L,Morgun E,Velluto D,He Y,Xu Q,Wang CR,Scott EA

    更新日期:2018-11-27 00:00:00

  • A Conformational Change in C-Reactive Protein Enhances Leukocyte Recruitment and Reactive Oxygen Species Generation in Ischemia/Reperfusion Injury.

    abstract:Introduction:C-reactive protein circulates as a pentameric protein (pCRP). pCRP is a well-established diagnostic marker as plasma levels rise in response to tissue injury and inflammation. We recently described pro-inflammatory properties of CRP, which are mediated by conformational changes from pCRP to bioactive isofo...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.00675

    authors: Thiele JR,Zeller J,Kiefer J,Braig D,Kreuzaler S,Lenz Y,Potempa LA,Grahammer F,Huber TB,Huber-Lang M,Bannasch H,Stark GB,Peter K,Eisenhardt SU

    更新日期:2018-04-16 00:00:00

  • Hemophilia A Inhibitor Subjects Show Unique PBMC Gene Expression Profiles That Include Up-Regulated Innate Immune Modulators.

    abstract::Formation of pathological anti-FVIII antibodies, or "inhibitors," is the most serious complication of therapeutic FVIII infusions, affecting up to 1/3 of severe Hemophilia A (HA) patients. Inhibitor formation is a classical T-cell dependent adaptive immune response. As such, it requires help from the innate immune sys...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.01219

    authors: Karim AF,Soltis AR,Sukumar G,Königs C,Ewing NP,Dalgard CL,Wilkerson MD,Pratt KP

    更新日期:2020-06-12 00:00:00

  • Multiple Variables at the Leukocyte Cell Surface Impact Fc γ Receptor-Dependent Mechanisms.

    abstract::Fc γ receptors (FcγR) expressed on the surface of human leukocytes bind clusters of immunoglobulin G (IgG) to induce a variety of responses. Many therapeutic antibodies and vaccine-elicited antibodies prevent or treat infectious diseases, cancers and autoimmune disorders by binding FcγRs, thus there is a need to fully...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.00223

    authors: Patel KR,Roberts JT,Barb AW

    更新日期:2019-02-14 00:00:00

  • Crispr/Cas Mediated Deletion of PTPN22 in Jurkat T Cells Enhances TCR Signaling and Production of IL-2.

    abstract::A single nucleotide polymorphism, C1858T, in the gene encoding the protein tyrosine phosphatase nonreceptor type 22 (PTPN22) results in one of the strongest genetic traits associated with autoimmune disease outside of the Major Histocompatibility Complex (MHC) genes. However, the consequences of this polymorphism, whi...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.02595

    authors: Bray C,Wright D,Haupt S,Thomas S,Stauss H,Zamoyska R

    更新日期:2018-11-12 00:00:00

  • IFN signaling: how a non-canonical model led to the development of IFN mimetics.

    abstract::The classical model of cytokine signaling dominates our view of specific gene activation by cytokines such as the interferons (IFNs). The importance of the model extends beyond cytokines and applies to hormones such as growth hormone (GH) and insulin, and growth factors such as epidermal growth factor (EGF) and fibrob...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2013.00202

    authors: Johnson HM,Noon-Song EN,Dabelic R,Ahmed CM

    更新日期:2013-07-25 00:00:00

  • Semaphorins in Angiogenesis and Autoimmune Diseases: Therapeutic Targets?

    abstract::The axonal guidance molecules, semaphorins, have been described to function both physiologically and pathologically outside of the nervous system. In this review, we focus on the vertebrate semaphorins found in classes 3 through 7 and their roles in vascular development and autoimmune diseases. Recent studies indicate...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.00346

    authors: Iragavarapu-Charyulu V,Wojcikiewicz E,Urdaneta A

    更新日期:2020-03-05 00:00:00

  • The role of natural killer cells in multiple sclerosis and their therapeutic implications.

    abstract::Multiple sclerosis (MS) is assumed to be an autoimmune disease initiated by autoreactive T cells that recognize central nervous system antigens. Although adaptive immunity is clearly involved in MS pathogenesis, innate immunity increasingly appears to be implicated in the disease. We and others have presented evidence...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2013.00063

    authors: Chanvillard C,Jacolik RF,Infante-Duarte C,Nayak RC

    更新日期:2013-03-13 00:00:00

  • The Interaction Mechanism Between Herpes Simplex Virus 1 Glycoprotein D and Host Antiviral Protein Viperin.

    abstract::Viperin is an interferon-inducible protein that responsible for a variety of antiviral responses to different viruses. Our previous study has shown that the ribonuclease UL41 of herpes simplex virus 1 (HSV-1) can degrade the mRNA of viperin to promote HSV-1 replication. However, it is not clear whether other HSV-1 enc...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.02810

    authors: Li M,Liao Z,Xu Z,Zou X,Wang Y,Peng H,Li Y,Ou X,Deng Y,Guo Y,Gan W,Peng T,Chen D,Cai M

    更新日期:2019-12-11 00:00:00

  • High TLR7 Expression Drives the Expansion of CD19+CD24hiCD38hi Transitional B Cells and Autoantibody Production in SLE Patients.

    abstract::Signaling through Toll-like receptor 7 (TLR7) drives the production of type I IFN and promotes the activation of autoreactive B cells and is implicated in the pathogenesis of systemic lupus erythematosus (SLE). While TLR7 has been extensively studied in murine lupus, much less is known about its role in the pathogenes...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.01243

    authors: Wang T,Marken J,Chen J,Tran VB,Li QZ,Li M,Cerosaletti K,Elkon KB,Zeng X,Giltiay NV

    更新日期:2019-06-04 00:00:00

  • Twenty Novel Disease Group-Specific and 12 New Shared Macrophage Pathways in Eight Groups of 34 Diseases Including 24 Inflammatory Organ Diseases and 10 Types of Tumors.

    abstract::The mechanisms underlying pathophysiological regulation of tissue macrophage (Mφ) subsets remain poorly understood. From the expression of 207 Mφ genes comprising 31 markers for 10 subsets, 45 transcription factors (TFs), 56 immunometabolism enzymes, 23 trained immunity (innate immune memory) enzymes, and 52 other gen...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.02612

    authors: Lai B,Wang J,Fagenson A,Sun Y,Saredy J,Lu Y,Nanayakkara G,Yang WY,Yu D,Shao Y,Drummer C 4th,Johnson C,Saaoud F,Zhang R,Yang Q,Xu K,Mastascusa K,Cueto R,Fu H,Wu S,Sun L,Zhu P,Qin X,Yu J,Fan D,Shen YH,Su

    更新日期:2019-11-14 00:00:00

  • Application of MultiStem(®) Allogeneic Cells for Immunomodulatory Therapy: Clinical Progress and Pre-Clinical Challenges in Prophylaxis for Graft Versus Host Disease.

    abstract::The last decade has seen much progress in adjunctive cell therapy for immune disorders. Both corporate and institutional Phase III studies have been run using mesenchymal stromal cells (MSC) for treatment of Graft versus Host Disease (GvHD), and product approval has been achieved for treatment of pediatric GvHD in Can...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2012.00345

    authors: Vaes B,Van't Hof W,Deans R,Pinxteren J

    更新日期:2012-11-27 00:00:00

  • Comprehensive Characterization of a Next-Generation Antiviral T-Cell Product and Feasibility for Application in Immunosuppressed Transplant Patients.

    abstract::Viral infections have a major impact on morbidity and mortality of immunosuppressed solid organ transplant (SOT) patients because of missing or failure of adequate pharmacologic antiviral treatment. Adoptive antiviral T-cell therapy (AVTT), regenerating disturbed endogenous T-cell immunity, emerged as an attractive al...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.01148

    authors: Amini L,Vollmer T,Wendering DJ,Jurisch A,Landwehr-Kenzel S,Otto NM,Jürchott K,Volk HD,Reinke P,Schmueck-Henneresse M

    更新日期:2019-05-28 00:00:00

  • Expression of T-Bet, Eomesodermin, and GATA-3 Correlates With Distinct Phenotypes and Functional Properties in Porcine γδ T Cells.

    abstract::Unlike mice and humans, porcine γδ T cells represent a prominent subset of T cells in blood and secondary lymphatic organs. GATA-3, T-bet and Eomesodermin (Eomes) are transcription factors with crucial functions in T-cell development and functional differentiation, but their expression has not been investigated in por...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00396

    authors: Rodríguez-Gómez IM,Talker SC,Käser T,Stadler M,Reiter L,Ladinig A,Milburn JV,Hammer SE,Mair KH,Saalmüller A,Gerner W

    更新日期:2019-03-11 00:00:00

  • Thermodynamics of Peptide-MHC Class II Interactions: Not all Complexes are Created Equal.

    abstract::The adaptive immune response begins when CD4+ T cells recognize antigenic peptides bound to class II molecules of the Major Histocompatibility Complex (MHCII). The interaction between peptides and MHCII has been historically interpreted as a rigid docking event. However, this model has been challenged by the evidence ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2013.00308

    authors: Ferrante A

    更新日期:2013-10-01 00:00:00

  • Pronounced Diurnal Pattern of Salivary C-Reactive Protein (CRP) With Modest Associations to Circulating CRP Levels.

    abstract::C-reactive protein (CRP), a humoral component of the innate immune system with important functions in host-defense, is extensively used as a sensitive biomarker of systemic inflammation. During inflammation, hepatocyte-derived CRP rises dramatically in the blood due to increased interleukin-6 (IL-6) levels. Reliable d...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.607166

    authors: Wetterö J,von Löhneysen S,Cobar F,Kristenson M,Garvin P,Sjöwall C

    更新日期:2021-01-08 00:00:00

  • Inducers, Attractors and Modulators of CD4+ Treg Cells in Non-Small-Cell Lung Cancer.

    abstract::Lung cancer is the leading cause of cancer-associated deaths worldwide, with non-small cell-lung cancer (NSCLC) accounting for approximately 80% of cases. Immune escape has been demonstrated to play a key role in the initiation and progression of NSCLC, although the underlying mechanisms are diverse and their puzzling...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.00676

    authors: Xie M,Wei J,Xu J

    更新日期:2020-04-28 00:00:00

  • Divergent lncRNA GATA3-AS1 Regulates GATA3 Transcription in T-Helper 2 Cells.

    abstract::Long non-coding RNAs (lncRNAs) possess a diverse array of regulatory functions including activation and silencing of gene transcription, regulation of splicing, and coordinating epigenetic modifications. GATA3-AS1 is a divergent lncRNA gene neighboring GATA3. GATA3 is considered the master regulator of TH2 lineage com...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.02512

    authors: Gibbons HR,Shaginurova G,Kim LC,Chapman N,Spurlock CF 3rd,Aune TM

    更新日期:2018-10-29 00:00:00

  • Dermatomyositis and Immune-Mediated Necrotizing Myopathies: A Window on Autoimmunity and Cancer.

    abstract::Autoimmune myopathies (myositides) are strongly associated with malignancy. The link between myositis and cancer, originally noticed by Bohan and Peter in their classification in 1975 (1), has been evidenced by large population-based cohort studies and a recent meta-analysis. The numerous reports of cases in which the...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2017.00992

    authors: Aussy A,Boyer O,Cordel N

    更新日期:2017-08-21 00:00:00

  • Genetic Loss of LCK Kinase Leads to Acceleration of Chronic Lymphocytic Leukemia.

    abstract::Most patients with chronic lymphocytic leukemia (CLL) exhibit an indolent disease course and unresponsive B cell receptors (BCRs) exemplified by an anergic phenotype of their leukemic cells. In up to 5% of patients, CLL transforms from an indolent subtype to an aggressive form of B cell lymphoma (Richter's syndrome), ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.01995

    authors: Märklin M,Fuchs AR,Tandler C,Heitmann JS,Salih HR,Kauer J,Quintanilla-Martinez L,Wirths S,Kopp HG,Müller MR

    更新日期:2020-09-02 00:00:00