Smith2011 - Three Stage Innate Immune Response to a Pneumococcal Lung Infection

  public model
Model Identifier
BIOMD0000000924
Short description
Pneumococcal pneumonia is a leading cause of death and a major source of human morbidity. The initial immune response plays a central role in determining the course and outcome of pneumococcal disease. We combine bacterial titer measurements from mice infected with Streptococcus pneumoniae with mathematical modeling to investigate the coordination of immune responses and the effects of initial inoculum on outcome. To evaluate the contributions of individual components, we systematically build a mathematical model from three subsystems that describe the succession of defensive cells in the lung: resident alveolar macrophages, neutrophils and monocyte-derived macrophages. The alveolar macrophage response, which can be modeled by a single differential equation, can by itself rapidly clear small initial numbers of pneumococci. Extending the model to include the neutrophil response required additional equations for recruitment cytokines and host cell status and damage. With these dynamics, two outcomes can be predicted: bacterial clearance or sustained bacterial growth. Finally, a model including monocyte-derived macrophage recruitment by neutrophils suggests that sustained bacterial growth is possible even in their presence. Our model quantifies the contributions of cytotoxicity and immune-mediated damage in pneumococcal pathogenesis.
Format
SBML (L2V4)
Related Publication
  • Mathematical model of a three-stage innate immune response to a pneumococcal lung infection.
  • Smith AM, McCullers JA, Adler FR
  • Journal of theoretical biology , 5/ 2011 , Volume 276 , Issue 1 , pages: 106-116 , PubMed ID: 21300073
  • Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA. asmith@lanl.gov
  • Pneumococcal pneumonia is a leading cause of death and a major source of human morbidity. The initial immune response plays a central role in determining the course and outcome of pneumococcal disease. We combine bacterial titer measurements from mice infected with Streptococcus pneumoniae with mathematical modeling to investigate the coordination of immune responses and the effects of initial inoculum on outcome. To evaluate the contributions of individual components, we systematically build a mathematical model from three subsystems that describe the succession of defensive cells in the lung: resident alveolar macrophages, neutrophils and monocyte-derived macrophages. The alveolar macrophage response, which can be modeled by a single differential equation, can by itself rapidly clear small initial numbers of pneumococci. Extending the model to include the neutrophil response required additional equations for recruitment cytokines and host cell status and damage. With these dynamics, two outcomes can be predicted: bacterial clearance or sustained bacterial growth. Finally, a model including monocyte-derived macrophage recruitment by neutrophils suggests that sustained bacterial growth is possible even in their presence. Our model quantifies the contributions of cytotoxicity and immune-mediated damage in pneumococcal pathogenesis.
Contributors
Sarubini Kananathan, Ahmad Zyoud

Metadata information

is
BioModels Database MODEL1808280007
BIOMD0000000924
BioModels Database MODEL1808280007
isDescribedBy
PubMed 21300073
hasTaxon
Taxonomy Homo sapiens
hasProperty
Mathematical Modelling Ontology Ordinary differential equation model
Gene Ontology immune response
NCIt Inflammation
C157959
occursIn
Brenda Tissue Ontology lung

Curation status
Curated


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Model files

Smith2011_V1.xml SBML L2V4 representation of Smith2011 - Three Stage Innate Immune Response to a Pneumococcal Lung Infection_curated 70.25 KB Preview | Download

Additional files

Final Version (7).xml SBML L2V4 representation of Smith2011 - Three Stage Innate Immune Response to a Pneumococcal Lung Infection_Original 26.85 KB Preview | Download
Final Version (7).cps Copasi file for the model_orignal 61.65 KB Preview | Download
Smith2011_V1_Fig5.sedml sed-ml L1V2 Smith2011 - Three Stage Innate Immune Response to a Pneumococcal Lung Infection_ Figure 5-Curated 15.37 KB Preview | Download
Smith2011_V1.sedml sed-ml L1V2 Smith2011 - Three Stage Innate Immune Response to a Pneumococcal Lung Infection_ Figure 4-Curated 15.27 KB Preview | Download
Smith2011_V1.cps COPASI version 4.27 (Build 217) Smith2011 - Three Stage Innate Immune Response to a Pneumococcal Lung Infection_Curated 129.31 KB Preview | Download

  • Model originally submitted by : Sarubini Kananathan
  • Submitted: 28-Aug-2018 14:50:29
  • Last Modified: 26-Mar-2020 13:35:05
Revisions
  • Version: 6 public model Download this version
    • Submitted on: 26-Mar-2020 13:35:05
    • Submitted by: Ahmad Zyoud
    • With comment: Automatically added model identifier BIOMD0000000924
  • Version: 4 public model Download this version
    • Submitted on: 28-Aug-2018 14:50:29
    • Submitted by: Sarubini Kananathan
    • With comment: Edited model metadata online.
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Curator's comment:
(added: 26 Mar 2020, 13:34:28, updated: 26 Mar 2020, 13:34:28)
The Figures 4a,4b,4a has been exactly reproduced. The rest of the figures within figure 4 are expressing same trend except for a slight difference Figure 5 is totally reproduced except with a slight shift in the X-axis