Carbo2013 - Mucosal Immune Response during H.pylori Infection

Model Identifier

BIOMD0000000480

Short description

Format

SBML (L2V4)

Related Publication

Predictive computational modeling of the mucosal immune responses during Helicobacter pylori infection.
Carbo A, Bassaganya-Riera J, Pedragosa M, Viladomiu M, Marathe M, Eubank S, Wendelsdorf K, Bisset K, Hoops S, Deng X, Alam M, Kronsteiner B, Mei Y, Hontecillas R.
PLoS ONE 2013; 8(9): e73365 2013 , DOI: 10.1371/journal.pone.0073365

Affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, Virginia, United States of America ; Center for Modeling Immunity to Enteric Pathogens Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, Virginia, United States of America.

Abstract: T helper (Th) cells play a major role in the immune response and pathology at the gastric mucosa during Helicobacter pylori infection. There is a limited mechanistic understanding regarding the contributions of CD4+ T cell subsets to gastritis development during H. pylori colonization. We used two computational approaches: ordinary differential equation (ODE)-based and agent-based modeling (ABM) to study the mechanisms underlying cellular immune responses to H. pylori and how CD4+ T cell subsets influenced initiation, progression and outcome of disease. To calibrate the model, in vivo experimentation was performed by infecting C57BL/6 mice intragastrically with H. pylori and assaying immune cell subsets in the stomach and gastric lymph nodes (GLN) on days 0, 7, 14, 30 and 60 post-infection. Our computational model reproduced the dynamics of effector and regulatory pathways in the gastric lamina propria (LP) in silico. Simulation results show the induction of a Th17 response and a dominant Th1 response, together with a regulatory response characterized by high levels of mucosal Treg) cells. We also investigated the potential role of peroxisome proliferator-activated receptor γ (PPARγ) activation on the modulation of host responses to H. pylori by using loss-of-function approaches. Specifically, in silico results showed a predominance of Th1 and Th17 cells in the stomach of the cell-specific PPARγ knockout system when compared to the wild-type simulation. Spatio-temporal, object-oriented ABM approaches suggested similar dynamics in induction of host responses showing analogous T cell distributions to ODE modeling and facilitated tracking lesion formation. In addition, sensitivity analysis predicted a crucial contribution of Th1 and Th17 effector responses as mediators of histopathological changes in the gastric mucosa during chronic stages of infection, which were experimentally validated in mice. These integrated immunoinformatics approaches characterized the induction of mucosal effector and regulatory pathways controlled by PPARγ during H. pylori infection affecting disease outcomes.

Contributors

Submitter of the first revision: Adria Carbo
Submitter of this revision: Lucian Smith
Curator: Lucian Smith
Modeller: Adria Carbo

Metadata information

is (2 statements)

BioModels Database BIOMD0000000480
BioModels Database MODEL1307130000

hasTaxon (1 statement)

Taxonomy Mus musculus

isVersionOf (3 statements)

Human Disease Ontology bacterial infectious disease
Gene Ontology T cell mediated immunity
Gene Ontology defense response to Gram-negative bacterium

isDescribedBy (1 statement)

DOI 10.1371/journal.pone.0073365

hasProperty (1 statement)

Mathematical Modelling Ontology Ordinary differential equation model

Curation status

Curated

Modelling approach(es)

ordinary differential equation model

Connected external resources

SBGN view in Newt Editor

Name	Description	Size	Actions
Model files (1)
BIOMD0000000480_url.xml	SBML L2V4 representation of Carbo2013 - Mucosal Immune Response during H.pylori Infection	338.55 KB	Preview \| Download
Additional files (13)
BIOMD0000000480-biopax2.owl	Auto-generated BioPAX (Level 2)	102.98 KB	Preview \| Download
BIOMD0000000480-biopax3.owl	Auto-generated BioPAX (Level 3)	166.06 KB	Preview \| Download
BIOMD0000000480-matlab.m	Auto-generated Matlab file.	38.86 KB	Preview \| Download
BIOMD0000000480.m	Auto-generated Octave file	38.86 KB	Preview \| Download
BIOMD0000000480.ode	Auto-generated ODE file for XPP.	32.81 KB	Preview \| Download
BIOMD0000000480.pdf	Auto-generated PDF file	630.09 KB	Preview \| Download
BIOMD0000000480.png	Auto-generated Reaction graph (PNG)	2.48 MB	Preview \| Download
BIOMD0000000480.svg	Auto-generated Reaction graph (SVG)	277.47 KB	Preview \| Download
BIOMD0000000480_url.sedml	CRBM auto-generated "template" SED-ML file.	135.45 KB	Preview \| Download
curation_image.png	Reproduced figure(s) from original curation.	21.90 KB	Preview \| Download
curation_notes.txt	Notes from original curation (describes curation_image).	155.00 Bytes	Preview \| Download
manifest.xml	Auto-generated manifest file for OMEX archives.	1.63 KB	Preview \| Download
metadata.rdf	Auto-generated annotation metadata file.	1.93 KB	Preview \| Download

Model originally submitted by : Adria Carbo
Submitted: Jul 13, 2013 1:54:30 AM
Last Modified: Aug 21, 2024 10:18:08 PM

Revisions

Version: 3
- Submitted on: Aug 21, 2024 10:18:08 PM
- Submitted by: Lucian Smith
- With comment: CRBM-sponsored manual and automated updates.
Version: 2
- Submitted on: Apr 8, 2016 6:37:09 PM
- Submitted by: Adria Carbo
- With comment: Current version of Carbo2013 - Mucosal Immune Response during H.pylori Infection
Version: 1
- Submitted on: Jul 13, 2013 1:54:30 AM
- Submitted by: Adria Carbo
- With comment: Original import of H. pylori Infection

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models

Species	Initial Concentration/Amount
species 14 T-helper 17 cell	1.0 item
species 15 lamina propria ; T-helper 17 cell	150000.0 item
s9 dendritic cell	1.0 item
s16 T-helper 17 cell	0.0 item
species 2 dendritic cell	5501140.56260765 item
species 3 macrophage	1000000.0 item
species 5 epithelial cell ; damaged	0.0 item
s25 dendritic cell	0.0 item

Reactions	Rate	Parameters
s28 => species_14; s28	k1*s28	k1=0.00214783
species_14 => ; species_14	c1k1species_14	k1=0.1
species_14 => species_15; species_14	c1k1species_14	k1=0.11695
species_1 + s6 => s9; species_1, s6	c2parameter_57species_1*s6	parameter_57 = 0.313385
s16 => s29; s16	parameter_16*s16	parameter_16 = 0.00858
species_2 = s9+species_1+s25+s4	[]	[]
species_3 = s22+s19+s21	[]	[]
s3 => species_5; s13, s16, s19, s3, s13, s16, s19	c4parameter_48s3(parameter_32s13+parameter_32s16+parameter_38s19)	parameter_48 = 1.0E-6; parameter_32 = 1.0E-4; parameter_38 = 1.0E-4
s16 => ; s16	c2parameter_64s16	parameter_64 = 0.1287
species_1 + s6 => s25; species_1, s6	c2parameter_58species_1*s6	parameter_58 = 5.0E-7

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Curator's comment:
(added: 17 Sep 2013, 13:04:49, updated: 17 Sep 2013, 13:04:49)

Figure 2A of the corresponding publication has been reproduced here. The model was simulated using SBML odeSolver and the plot was generated using Gnuplot.