BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000583?filename=BIOMD0000000583.pdfhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000583?filename=BIOMD0000000583-biopax3.owlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000583?filename=BIOMD0000000583-biopax2.owlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000583?filename=BIOMD0000000583_url.xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000583?filename=BIOMD0000000583_urn.xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000583?filename=BIOMD0000000583.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000583?filename=BIOMD0000000583.vcmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000583?filename=BIOMD0000000583.scihttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000583?filename=BIOMD0000000583.pnghttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000583?filename=BIOMD0000000583.xppprimaryOK200Andrew LeberManually curatedClostridium Difficile ColitisL2V4https://www.ebi.ac.uk/biomodels/BIOMD000000058326230099falseBioModelsSBMLModelsLeber2015 Mucosal immunity and gut microbiome interaction during C. difficile infection2015MODEL1507200000Leber A, Viladomiu M, Hontecillas R, Abedi V, Philipson C, Hoops S, Howard B, Bassaganya-Riera JLeber A26230099,
Clostridium difficile infections are associated with the use of broad-spectrum antibiotics and result in an exuberant inflammatory response, leading to nosocomial diarrhea, colitis and even death. To better understand the dynamics of mucosal immunity during C. difficile infection from initiation through expansion to resolution, we built a computational model of the mucosal immune response to the bacterium. The model was calibrated using data from a mouse model of C. difficile infection. The model demonstrates a crucial role of T helper 17 (Th17) effector responses in the colonic lamina propria and luminal commensal bacteria populations in the clearance of C. difficile and colonic pathology, whereas regulatory T (Treg) cells responses are associated with the recovery phase. In addition, the production of anti-microbial peptides by inflamed epithelial cells and activated neutrophils in response to C. difficile infection inhibit the re-growth of beneficial commensal bacterial species. Computational simulations suggest that the removal of neutrophil and epithelial cell derived anti-microbial inhibitions, separately and together, on commensal bacterial regrowth promote recovery and minimize colonic inflammatory pathology. Simulation results predict a decrease in colonic inflammatory markers, such as neutrophilic influx and Th17 cells in the colonic lamina propria, and length of infection with accelerated commensal bacteria re-growth through altered anti-microbial inhibition. Computational modeling provides novel insights on the therapeutic value of repopulating the colonic microbiome and inducing regulatory mucosal immune responses during C. difficile infection. Thus, modeling mucosal immunity-gut microbiota interactions has the potential to guide the development of targeted fecal transplantation therapies in the context of precision medicine interventions.. null, 10.
The Center for Modeling Immunity to Enteric Pathogens, Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, Virginia, United States of America; Nutritional Immunology and Molecular Medicine Laboratory (www.nimml.org), Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, Virginia, United States of America.ajleber@vbi.vt.eduVirginia TechBIOMD0000000583Clostridium difficile infections are associated with the use of broad-spectrum antibiotics and result in an exuberant inflammatory response, leading to nosocomial diarrhea, colitis and even death. To better understand the dynamics of mucosal immunity during C. difficile infection from initiation through expansion to resolution, we built a computational model of the mucosal immune response to the bacterium. The model was calibrated using data from a mouse model of C. difficile infection. The model demonstrates a crucial role of T helper 17 (Th17) effector responses in the colonic lamina propria and luminal commensal bacteria populations in the clearance of C. difficile and colonic pathology, whereas regulatory T (Treg) cells responses are associated with the recovery phase. In addition, the production of anti-microbial peptides by inflamed epithelial cells and activated neutrophils in response to C. difficile infection inhibit the re-growth of beneficial commensal bacterial species. Computational simulations suggest that the removal of neutrophil and epithelial cell derived anti-microbial inhibitions, separately and together, on commensal bacterial regrowth promote recovery and minimize colonic inflammatory pathology. Simulation results predict a decrease in colonic inflammatory markers, such as neutrophilic influx and Th17 cells in the colonic lamina propria, and length of infection with accelerated commensal bacteria re-growth through altered anti-microbial inhibition. Computational modeling provides novel insights on the therapeutic value of repopulating the colonic microbiome and inducing regulatory mucosal immune responses during C. difficile infection. Thus, modeling mucosal immunity-gut microbiota interactions has the potential to guide the development of targeted fecal transplantation therapies in the context of precision medicine interventions.Systems Modeling of Interactions between Mucosal Immunity and the Gut Microbiome during Clostridium difficile Infection.Leber Andrew A, Viladomiu Monica M, Hontecillas Raquel R, Abedi Vida V, Philipson Casandra C, Hoops Stefan S, Howard Brad B, Bassaganya-Riera Josep Jdigestive canal, Immune Processes, Immune Responses, AI747421, gut, Process, lower gastrointestinal tract, Gus-u, alimentary tract, Gus-t, Infestations and Infections, Gus-s, enteric tract, Gus-r, Infection and Infestation, Infections and Infestations., gut tube, Infestation and Infection, Gus, Gur, Immune Response, Immune, Gut, g, gastrointestinal system, lower GI tract, Response, Infection, digestive tube, asd, alimentary system, Immune Process, alimentary canalFecal Material Transplantation, antimicrobials, The runs, Resolution Property, Suggestion, REMOVAL, antimicrobial agents, growth and development, Glandular, End-Of-Life, Stool Transplant, Polymorphonuclear, dmTAF[[II]]230, Polypeptides, microbicides, Phenylethylbarbituric Acid, responsivity, neutrophil leukocyte, 6-trione, LE Cell, Response Inhibition, 4, Decreased, Activate, Neutrophil Band Cells, antimicrobial, A, TFIID TAF250, cel, diarrheal disease, Antibiotika, Reduced, result, Adenomatous Epithelial, Computational, Application Context, suppressor T-lymphocyte, Bacteria <bacteria>, Prokaryotae, Computational Technique, FMT, polymorphonuclear leukocyte, Role Concepts, Type 17 Helper T Cells, 6(1H, Medicine, Better, Infections and Infestations, Procaryotae, Add, dTAF[[II]]230, Micro-organism, Gut Microbiome, RECOVERY, TAF200, Microorganisms, Derived Flag, Resolution of Pathologic Process, Squamous, Extracted, alpha-beta regulatory T-lymphocyte, Neutrophil Band Cell, neutrophil granulocyte, Intestinal Microbiota, diarrheal disorder, Role Concept, Role, prokaryotes, CD25-positive, lamina propria of colonic mucosa, Diarrhoea, Adenomatous Epithelial Cells, 5H)-trione, Infection and Infestation, TH-17, Leading, Th17 cells, 5-ethyl-5-phenylpyrimidine-2, lamina propria mucosae of colon, Taf250, Theranostics, Cells, Polymorphonuclear Leukocytes, Pathology Resolution, Prokaryota, TAF230, Induced, polynuclear neutrophilic leukocyte, Band Cell, simulation, immune response in MALT, antibiotique, Remove, Potential, colonic lamina propria, PHENYLETHYLMALONYLUREA, Inhibition, Inducible, Cardiac, loose stools, It improved, Precision, Phenylethylbarbitursaeure, microflora, Inhibiting, dTAF[[II]]250, Individualized, Pathologic Process Resolution, Activation, cell, Clostridioides difficile infections, MUCOSA, lamina propria of colonic mucous membrane, CD4-positive, Inducing, Target, BETTER/IMPROVED/RECOVERING, inflammation, suppressor T cell, outcome, Solution, TH-17 Cell, Usage, dTAF250, Phenobarbitol, Use, Transitional Epithelial Cells, Resolve, peptidos, species, Predictive, microorganism, LE, Antibiotikum, Transitional, New, colitis, Squamous Cells, bacteria, Computer Modeling, Poop Transplant, Polymorphonuclear Neutrophils, Leukocytes, Predictive Medicine, Result, Preceding, INTERVENTIONS, BG:DS00004.13, Personalized, Cell, Polymorphonuclear Leukocyte, Concept, dTAF230, Addition, polypeptide, Mucosal, Cuboidal Glandular Epithelial Cells, immune response in mucosal-associated lymphoid tissue, post-mortem, TAF[[II]]250/230, Computation, Columnar Glandular Epithelial Cells, Induce, activate, Value, Death, epitheliocyte, Before, Phenylaethylbarbitursaeure, Watery stool, Taf[[II]]250, Destination, Regulator, postnatal growth, Theranostic, Intestinal Microbiome, Derived Value, recover, P-Health, prokaryote, alpha-beta regulatory T lymphocyte, PMN, polymorphonuclear leucocyte, biopsy, Microorganism, mucosa, Phenylethylbarbiturate, deceased, Derived, Epithelial Cell, single-organism developmental process, Individualized Medicine, postnatal development, Activated, Infestations and Infections, Cardiac Death, intestinal microflora, peptide, neutrophilic leucocyte, peptido, Guide Device, Roles, Mathematical Derivation, Concepts, TH-17 Cells, Inhibitory, Prior, cytopathology, immune response in urogenital tract, Immune Processes, Targeting, Immune Responses, Eubacteria, inflammatory response, T Helper 17 Cells, peptides, CDISC Interventions Class., Type 17 Helper T Cell, Diarrheas, IMPROVED, End Of Life, 5-ethyl-5-phenyl-2, regulatory T-cell, Employ, Context, Novel, Immune, A Mouse, polynuclear neutrophilic leucocyte, Pathologies, Clostridium difficile Infections, Therapies, DERIVED, Mathematical Models and Simulations, EXTRACTING, 3H, Outcome, associated, Single-Celled Organism, antibiotic, Transitional Epithelial Cell, Therapy, Pre, wide/broad, Process, inflammation of colon, Adenomatous, The trots, TAFII-250, TAF250/230, Microbial, Transitional Epithelial, results, DECREASED, neutrocyte, TAFII250, Induction, LE Cells, TH 17 Cells, epithelial, Personalized Medicine, regulatory T-lymphocyte, diarrhea of presumed infectious origin, microbicide, Near-Death Experience, Decrease, General, Adenomatous Epithelial Cell, Polymorphonuclear Neutrophil, Guide, Squamous Cell, histopathology, Derivation, growth pattern, neutrophilic granulocyte, Determination of Death, Mucous Membrane, non-developmental growth, Modeling, gut flora, 5-Ethyl-5-phenyl-pyrimidine-2, initiation, Improved, CG17603, TAF[[II]], TH 17 Cell, Treatments, C. diff Infections, wide, SR3-5, Polypeptide, Phenylethylmalonylurea, d230, frequent stools, Computed, dTAFII250, eubacteria, Glandular Epithelial, broad, EfW1, Squamous Epithelial Cells, dmTAF1, Taf230, phenobarbital, colon inflammation, Squamous Epithelial, antibiotics, Mucosal Immunity, TAF250, Epithelial, reactivity, Taf200, alpha-beta regulatory T-cell, Computing, Suggest, Promotion, neutrophil leucocyte, Better than Others, Reduction, 5-Phenyl-5-ethylbarbituric acid, Taf1p, neutrophilic leukocyte, Monera, mucous membrane, Infestation and Infection, Immune Response, 5H)-pyrimidinetrione, Epithelial Cells, Promote, Physiologic Resolution, gut microflora, fungi, TAF, Colitides, Squamous Epithelial Cell, Immune Process, Neutrophil, Glandular Epithelial Cell, Removal, data, regulatory T lymphocyte, TAF[[II]]250, Leukocyte, Mucosa, Regulatory, Recovery, Promoting, Targeted, l(3)84Ab, Fecal Transplantation, Th17 Cell, Production, diarrhoea of presumed infectious origin, Resolved, Extraction, Th17, Peptide, Intestinal Flora, intestinal flora, development, colitis (disease), Phenobarbituric Acid, Diarrhea, DRVFL, p230, diarrhea, Fecal Microbiota Transplantation, Infection, Phenobarbital, TFIID, Gut Microbiota, Resolution, death, Luminal, TAF[[II]]230, suppressor T lymphocyte, diarrhoea, 5-Ethyl-5-phenylbarbituric acid, Salvage, Glandular Epithelial Cells, TAF[II]250, value, suppressor T-cell, DmelCG17603, Treg, Therapeutic, DER, Response, BEFORE, Microbe, Peptid, Treatment, P Health, Interventions, Simulation, T Helper 17 Cell, response, poly, Experimental Result, growth, Poo Transplant, polymorphonuclear neutrophil, Phenobarbitone, TAF1extent, Phenylethylbarbiturate, deceased, Public Sectors, Epithelial Cell, CDI, single-organism developmental process, antimicrobials, The runs, Individualized Medicine, postnatal development, Infestations and Infections, antimicrobial agents, growth and development, Cardiac Death, Glandular, End-Of-Life, Polymorphonuclear, dmTAF[[II]]230, peptide, Polypeptides, microbicides, Clostridium difficile, neutrophilic leucocyte, Phenylethylbarbituric Acid, peptido, Roles, responsivity, neutrophil leukocyte, Concepts, 6-trione, LE Cell, 4, TH-17 Cells, cytopathology, Public Enterprise, immune response in urogenital tract, Neutrophil Band Cells, antimicrobial, Immune Processes, Immune Responses, Eubacteria, grafting, inflammatory response, T Helper 17 Cells, TFIID TAF250, peptides, cel, diarrheal disease, Type 17 Helper T Cell, Antibiotika, Diarrheas, Microbial Community Structure, Public Domains, alimentary tract, End Of Life, Adenomatous Epithelial, 5-ethyl-5-phenyl-2, regulatory T-cell, Immune, suppressor T-lymphocyte, g, Bacteria <bacteria>, Prokaryotae, polymorphonuclear leukocyte, polynuclear neutrophilic leucocyte, Role Concepts, Pathologies, Type 17 Helper T Cells, 6(1H, Microbial Community Structures, Medicine, digestive tube, asd, Infections and Infestations, 3H, Procaryotae, house mouse, associated, alimentary system, antibiotic, Transitional Epithelial Cell, dTAF[[II]]230, wide/broad, Process, completeness, lower gastrointestinal tract, mouse, inflammation of colon, TAF200, Adenomatous, The trots, Squamous, TAFII-250, TAF250/230, Microbial, Transitional Epithelial, results, alpha-beta regulatory T-lymphocyte, Neutrophil Band Cell, neutrophil granulocyte, neutrocyte, TAFII250, diarrheal disorder, Role Concept, LE Cells, TH 17 Cells, epithelial, Personalized Medicine, Public Domain, regulatory T-lymphocyte, diarrhea of presumed infectious origin, Role, Domains, microbicide, Near-Death Experience, prokaryotes, CD25-positive, lamina propria of colonic mucosa, Diarrhoea, Microbial Communities, Domain, Adenomatous Epithelial Cell, Polymorphonuclear Neutrophil, Adenomatous Epithelial Cells, AI747421, Squamous Cell, histopathology, growth pattern, neutrophilic granulocyte, Microbial Community Compositions, Determination of Death, mice, non-developmental growth, 5-Ethyl-5-phenyl-pyrimidine-2, initiation, 5H)-trione, Infection and Infestation, CG17603, TAF[[II]], TH 17 Cell, TH-17, Composition, wide, 5-ethyl-5-phenylpyrimidine-2, Sector, lamina propria mucosae of colon, Taf250, gastrointestinal system, SR3-5, Theranostics, Cells, Polymorphonuclear Leukocytes, Mouse, Polypeptide, Phenylethylmalonylurea, grafts, Human Microbiomes, Prokaryota, TAF230, Community, digestive canal, polynuclear neutrophilic leukocyte, Microbial Community Composition, d230, Sectors, Band Cell, immune response in MALT, antibiotique, frequent stools, colonic lamina propria, number, enteric tract, dTAFII250, Copyrights, eubacteria, Glandular Epithelial, broad, PHENYLETHYLMALONYLUREA, Transplantations, EfW1, presence, Human, Gus, Gur, Cardiac, Gut, Squamous Epithelial Cells, loose stools, dmTAF1, Taf230, phenobarbital, Precision, colon inflammation, Phenylethylbarbitursaeure, Enterprises, Squamous Epithelial, antibiotics, TAF250, Epithelial, clostridium difficile disease, reactivity, Taf200, gut, dTAF[[II]]250, Individualized, alpha-beta regulatory T-cell, cell, neutrophil leucocyte, lamina propria of colonic mucous membrane, CD4-positive, 5-Phenyl-5-ethylbarbituric acid, inflammation, Taf1p, neutrophilic leukocyte, Public Enterprises, Monera, suppressor T cell, TH-17 Cell, dTAF250, Infestation and Infection, Phenobarbitol, Immune Response, Abstract, 5H)-pyrimidinetrione, Epithelial Cells, lower GI tract, Transitional Epithelial Cells, peptidos, fungi, species, Predictive, TAF, Enterprise, Immune Process, Colitides, Squamous Epithelial Cell, LE, Neutrophil, Glandular Epithelial Cell, Human Microbiome, Antibiotikum, Transitional, colitis, Squamous Cells, data, bacteria, regulatory T lymphocyte, TAF[[II]]250, Leukocyte, Community Composition, Polymorphonuclear Neutrophils, Leukocytes, Predictive Medicine, l(3)84Ab, Th17 Cell, BG:DS00004.13, Personalized, diarrhoea of presumed infectious origin, Cell, Peptide, Polymorphonuclear Leukocyte, Th17, Concept, dTAF230, polypeptide, development, gut tube, colitis (disease), count in organism, Phenobarbituric Acid, Diarrhea, Cuboidal Glandular Epithelial Cells, Mus, Public, p230, diarrhea, immune response in mucosal-associated lymphoid tissue, Bacillus difficilis, post-mortem, Infection, TAF[[II]]250/230, Phenobarbital, TFIID, Columnar Glandular Epithelial Cells, Death, alimentary canal, epitheliocyte, Data Base, Microbiome, Phenylaethylbarbitursaeure, Watery stool, Taf[[II]]250, death, Luminal, TAF[[II]]230, Microbiomes, suppressor T lymphocyte, diarrhoea, Microbial Community, 5-Ethyl-5-phenylbarbituric acid, postnatal growth, Gus-u, Community Structure, Gus-t, Glandular Epithelial Cells, Gus-s, Gus-r, TAF[II]250, Theranostic, [Clostridium] difficile, suppressor T-cell, DmelCG17603, Treg, P-Health, prokaryote, Response, alpha-beta regulatory T lymphocyte, PMN, polymorphonuclear leucocyte, Microbiotas, Peptid, P Health, Public., T Helper 17 Cell, response, quantitative, biopsy, poly, growth, polymorphonuclear neutrophil, Phenobarbitone, TAF1, presence or absence in organismclostridium difficile disease, Intestinal Microbiota, Gut Microbiome, Modeling, gut flora, gut microflora, Gut Microbiota, intestinal microflora, CDI., Intestinal Microbiome, Mucosal Immunity, Intestinal Flora, microflora, intestinal florafalseLeber2015 - Mucosal immunity and gut microbiome interaction during C. difficile infection
Leber2015 - Mucosal immunity and gut
microbiome interaction during C. difficile infection
This model is described in the article:
Systems Modeling of
Interactions between Mucosal Immunity and the Gut Microbiome
during Clostridium difficile Infection.
Leber A, Viladomiu M, Hontecillas R,
Abedi V, Philipson C, Hoops S, Howard B, Bassaganya-Riera
J.
PLoS ONE 2015; 10(7): e0134849
Abstract:
Clostridium difficile infections are associated with the use
of broad-spectrum antibiotics and result in an exuberant
inflammatory response, leading to nosocomial diarrhea, colitis
and even death. To better understand the dynamics of mucosal
immunity during C. difficile infection from initiation through
expansion to resolution, we built a computational model of the
mucosal immune response to the bacterium. The model was
calibrated using data from a mouse model of C. difficile
infection. The model demonstrates a crucial role of T helper 17
(Th17) effector responses in the colonic lamina propria and
luminal commensal bacteria populations in the clearance of C.
difficile and colonic pathology, whereas regulatory T (Treg)
cells responses are associated with the recovery phase. In
addition, the production of anti-microbial peptides by inflamed
epithelial cells and activated neutrophils in response to C.
difficile infection inhibit the re-growth of beneficial
commensal bacterial species. Computational simulations suggest
that the removal of neutrophil and epithelial cell derived
anti-microbial inhibitions, separately and together, on
commensal bacterial regrowth promote recovery and minimize
colonic inflammatory pathology. Simulation results predict a
decrease in colonic inflammatory markers, such as neutrophilic
influx and Th17 cells in the colonic lamina propria, and length
of infection with accelerated commensal bacteria re-growth
through altered anti-microbial inhibition. Computational
modeling provides novel insights on the therapeutic value of
repopulating the colonic microbiome and inducing regulatory
mucosal immune responses during C. difficile infection. Thus,
modeling mucosal immunity-gut microbiota interactions has the
potential to guide the development of targeted fecal
transplantation therapies in the context of precision medicine
interventions.
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2015-08-282014-04-082015-07-20BIOMD000000058326230099MODEL1507200000BIOMD0000000583GO:0030383GO:0006955FMA:145861009014962BTO:0000416BTO:0002330BTO:0000767BTO:0002042BTO:0000130BTO:0000414BTO:0000801BTO:0005655BTO:0001678BTO:0004520BTO:000782