Mathematical model of a three-stage innate immune response to a pneumococcal lung infection

Amber Smith, Jonathan Mccullers, Frederick R. Adler

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)106-116
Number of pages11
JournalJournal of Theoretical Biology
Volume276
Issue number1
DOIs
StatePublished - May 7 2011

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Pneumococcal Infections
Macrophage
Immune Response
Alveolar Macrophages
Streptococcus pneumoniae
Lung
Neutrophils
Innate Immunity
Infection
macrophages
Theoretical Models
mathematical models
Macrophages
lungs
Mathematical Model
Monocytes
Mathematical models
Pneumococcal Pneumonia
neutrophils
Neutrophil Infiltration

All Science Journal Classification (ASJC) codes

  • Statistics and Probability
  • Modeling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

Cite this

Mathematical model of a three-stage innate immune response to a pneumococcal lung infection. / Smith, Amber; Mccullers, Jonathan; Adler, Frederick R.

In: Journal of Theoretical Biology, Vol. 276, No. 1, 07.05.2011, p. 106-116.

Research output: Contribution to journalArticle

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