Constraint-based network model of pathogen-immune system interactions

Juilee Thakar, Assieh Saadatpour-Moghaddam, Eric Thomas Harvill, Reka Z. Albert

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Pathogenic bacteria such as Bordetella bronchiseptica modulate host immune responses to enable their establishment and persistence; however, the immune response is generally successful in clearing these bacteria. Here, we model the dynamic outcome of the interplay between host immune components and B. bronchiseptica virulence factors. The model extends our previously published interaction network of B. bronchiseptica and includes the existing experimental information on the relative timing of IL10 and IFNg activation in the form of qualitative inequalities. The current model improves the previous one in two directions: (i) by augmenting the network with new nodes with specific function in T helper cell differentiation and effector mechanisms and (ii) by using a dynamic approach that allows us to quantify node states and mechanisms revealed to be important from our previous model. The model makes predictions about the time scales of each process, the activity thresholds of each node and novel regulatory interactions. For example, the model predicts that the activity threshold of IL4 is higher than that of IL12 and that pro-inflammatory cytokines regulate the activity of Th2 cells. Some of these predictions are supported by the literature, and many can serve as targets of future experiments.

Original languageEnglish (US)
Pages (from-to)599-612
Number of pages14
JournalJournal of the Royal Society Interface
Volume6
Issue number36
DOIs
StatePublished - Jul 6 2009

Fingerprint

Bordetella bronchiseptica
Immune system
Pathogens
Bordetella Virulence Factors
Immune System
Bacteria
Th2 Cells
Interleukin-12
Interleukin-4
Interleukin-10
Cell Differentiation
Cytokines
Virulence Factors
Chemical activation

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biophysics
  • Bioengineering
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering

Cite this

Thakar, Juilee ; Saadatpour-Moghaddam, Assieh ; Harvill, Eric Thomas ; Albert, Reka Z. / Constraint-based network model of pathogen-immune system interactions. In: Journal of the Royal Society Interface. 2009 ; Vol. 6, No. 36. pp. 599-612.
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Constraint-based network model of pathogen-immune system interactions. / Thakar, Juilee; Saadatpour-Moghaddam, Assieh; Harvill, Eric Thomas; Albert, Reka Z.

In: Journal of the Royal Society Interface, Vol. 6, No. 36, 06.07.2009, p. 599-612.

Research output: Contribution to journalArticle

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