A spatial model of the efficiency of T cell search in the influenza-infected lung

Drew Levin, Stephanie Forrest, Soumya Banerjee, Candice Clay, Judy Cannon, Melanie Moses, Frederick Koster

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Emerging strains of influenza, such as avian H5N1 and 2009 pandemic H1N1, are more virulent than seasonal H1N1 influenza, yet the underlying mechanisms for these differences are not well understood. Subtle differences in how a given strain interacts with the immune system are likely a key factor in determining virulence. One aspect of the interaction is the ability of T cells to locate the foci of the infection in time to prevent uncontrolled expansion. Here, we develop an agent based spatial model to focus on T cell migration from lymph nodes through the vascular system to sites of infection. We use our model to investigate whether different strains of influenza modulate this process. We calibrate the model using viral and chemokine secretion rates we measure in vitro together with values taken from literature. The spatial nature of the model reveals unique challenges for T cell recruitment that are not apparent in standard differential equation models. In this model comparing three influenza viruses, plaque expansion is governed primarily by the replication rate of the virus strain, and the efficiency of the T cell search-and-kill is limited by the density of infected epithelial cells in each plaque. Thus for each virus there is a different threshold of T cell search time above which recruited T cells are unable to control further expansion. Future models could use this relationship to more accurately predict control of the infection.

Original languageEnglish (US)
Pages (from-to)52-63
Number of pages12
JournalJournal of Theoretical Biology
Volume398
DOIs
StatePublished - Jun 7 2016
Externally publishedYes

Fingerprint

T-cells
Influenza
Spatial Model
Lung
influenza
Human Influenza
T-lymphocytes
lungs
T-Lymphocytes
Virus
Infection
Viruses
Model
Cell Migration
Secretion
Agent-based Model
Immune System
viruses
Pandemics
Infection Control

Keywords

  • Agent-based model
  • Computational biology
  • Immunology
  • Systems biology
  • Virology

ASJC Scopus subject areas

  • 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

A spatial model of the efficiency of T cell search in the influenza-infected lung. / Levin, Drew; Forrest, Stephanie; Banerjee, Soumya; Clay, Candice; Cannon, Judy; Moses, Melanie; Koster, Frederick.

In: Journal of Theoretical Biology, Vol. 398, 07.06.2016, p. 52-63.

Research output: Contribution to journalArticle

Levin, Drew ; Forrest, Stephanie ; Banerjee, Soumya ; Clay, Candice ; Cannon, Judy ; Moses, Melanie ; Koster, Frederick. / A spatial model of the efficiency of T cell search in the influenza-infected lung. In: Journal of Theoretical Biology. 2016 ; Vol. 398. pp. 52-63.
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