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
Submitter of the first revision: Sarubini Kananathan
Submitter of this revision: Ahmad Zyoud
Modellers: Sarubini Kananathan, Ahmad Zyoud

Metadata information

is (3 statements)
BioModels Database MODEL1808280007
BioModels Database BIOMD0000000924
BioModels Database MODEL1808280007

isDescribedBy (1 statement)
PubMed 21300073

hasTaxon (1 statement)
Taxonomy Homo sapiens

hasProperty (4 statements)
Mathematical Modelling Ontology Ordinary differential equation model
Gene Ontology immune response
NCIt Inflammation
NCIt Pneumococcal Pneumonia

occursIn (1 statement)
Brenda Tissue Ontology lung

Curation status
Curated
Modelling approach(es)
ordinary differential equation model
Tags

Connected external resources

SBGN view in Newt Editor

Name Description Size Actions

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).cps Copasi file for the model_orignal 61.65 KB Preview | Download
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
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
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_Fig5.sedml sed-ml L1V2 Smith2011 - Three Stage Innate Immune Response to a Pneumococcal Lung Infection_ Figure 5-Curated 15.37 KB Preview | Download

  • Model originally submitted by : Sarubini Kananathan
  • Submitted: Aug 28, 2018 2:50:29 PM
  • Last Modified: Mar 26, 2020 1:35:05 PM
Revisions
  • Version: 6 public model Download this version
    • Submitted on: Mar 26, 2020 1:35:05 PM
    • Submitted by: Ahmad Zyoud
    • With comment: Automatically added model identifier BIOMD0000000924
  • Version: 4 public model Download this version
    • Submitted on: Aug 28, 2018 2:50:29 PM
    • Submitted by: Sarubini Kananathan
    • With comment: Edited model metadata online.

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 Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
Neutrophils N

0010527 		0.0 mmol
Susceptible epithelial cells EU

0006083 		1.0E8 mmol
proinflammatory cytokine C

Cytokine 		0.0 mmol
Epithelial cells with bacteria attached Ea

infected cell 		0.0 mmol
Pneumococci P

C76384 		100000.0 mmol
Debris D

C120869 		0.0 mmol
Reactions
Reactions Rate Parameters
=> Neutrophils__N; proinflammatory_cytokine__C compartment*eta*proinflammatory_cytokine__C*(1-Neutrophils__N/N_max) eta = 1.33; N_max = 180000.0
Susceptible_epithelial_cells__EU => ; Pneumococci___P compartment*omega*Pneumococci___P*Susceptible_epithelial_cells__EU omega = 2.1E-8
=> proinflammatory_cytokine__C; Epithelial_cells_with_bacteria_attached__Ea, Neutrophils__N, Pneumococci___P compartment*(alpha*Epithelial_cells_with_bacteria_attached__Ea/(1+k_n*Neutrophils__N)+v*theta_M*Pneumococci___P*M_Astar/(d+kappa+theta_M*Pneumococci___P*(1+k_n*Neutrophils__N))) theta_M = 4.2E-8; d = 0.001; k_n = 1.4E-5; M_Astar = 1000000.0; alpha = 0.021; v = 0.029; kappa = 0.042
=> Epithelial_cells_with_bacteria_attached__Ea; Pneumococci___P, Susceptible_epithelial_cells__EU compartment*omega*Pneumococci___P*Susceptible_epithelial_cells__EU omega = 2.1E-8
=> Pneumococci___P compartment*r*Pneumococci___P*(1-Pneumococci___P/K_P) K_P = 3.41765197726012E8; r = 1.13
Neutrophils__N => ; Pneumococci___P compartment*(d_NP*Neutrophils__N*Pneumococci___P+d_N*Neutrophils__N) d_NP = 1.76E-7; d_N = 0.063
Debris__D => compartment*d_D*Debris__D*M_Astar d_D = 1.4E-7; M_Astar = 1000000.0
=> Debris__D; Neutrophils__N, Pneumococci___P, Epithelial_cells_with_bacteria_attached__Ea compartment*(rho1*d_NP*Neutrophils__N*Pneumococci___P+rho2*d_N*Neutrophils__N+rho3*d_E*Epithelial_cells_with_bacteria_attached__Ea) d_NP = 1.76E-7; d_E = 0.167; rho1 = 0.15; d_N = 0.063; rho2 = 0.001; rho3 = 1.0E-5
Epithelial_cells_with_bacteria_attached__Ea => compartment*d_E*Epithelial_cells_with_bacteria_attached__Ea d_E = 0.167
proinflammatory_cytokine__C => compartment*d_C*proinflammatory_cytokine__C d_C = 0.83
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