Carbo2013 - Mucosal Immune Response during H.pylori Infection

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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
  • 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.
  • 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.
Adria Carbo

Metadata information

BioModels Database MODEL1307130000
BioModels Database BIOMD0000000480
Taxonomy Mus musculus
Mathematical Modelling Ontology Ordinary differential equation model
Curation status
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BIOMD0000000480_url.xml SBML L2V4 representation of Carbo2013 - Mucosal Immune Response during H.pylori Infection 330.79 KB Preview | Download

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  • Model originally submitted by : Adria Carbo
  • Submitted: Jul 13, 2013 1:54:30 AM
  • Last Modified: Apr 8, 2016 6:37:09 PM
  • Version: 2 public model Download this version
    • 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 public model Download this version
    • Submitted on: Jul 13, 2013 1:54:30 AM
    • Submitted by: Adria Carbo
    • With comment: Original import of H. pylori Infection
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.