A mathematical model of CR3/TLR2 crosstalk in the context of Francisella tularensis infection.
Complement Receptor 3 (CR3) and Toll-like Receptor 2 (TLR2) are pattern recognition receptors expressed on the surface of human macrophages. Although these receptors are essential components for recognition by the innate immune system, pathogen coordinated crosstalk between them can suppress the pro...
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2012-01-01
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doaj-66547be67da0495b9c21c01f3ec8d6cb2021-04-21T15:42:37ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582012-01-01811e100275710.1371/journal.pcbi.1002757A mathematical model of CR3/TLR2 crosstalk in the context of Francisella tularensis infection.Rachel LeanderShipan DaiLarry S SchlesingerAvner FriedmanComplement Receptor 3 (CR3) and Toll-like Receptor 2 (TLR2) are pattern recognition receptors expressed on the surface of human macrophages. Although these receptors are essential components for recognition by the innate immune system, pathogen coordinated crosstalk between them can suppress the production of protective cytokines and promote infection. Recognition of the virulent Schu S4 strain of the intracellular pathogen Francisella tularensis by host macrophages involves CR3/TLR2 crosstalk. Although experimental data provide evidence that Lyn kinase and PI3K are essential components of the CR3 pathway that influences TLR2 activity, additional responsible upstream signaling components remain unknown. In this paper we construct a mathematical model of CR3 and TLR2 signaling in response to F. tularensis. After demonstrating that the model is consistent with experimental results we perform numerical simulations to evaluate the contributions that Akt and Ras-GAP make to ERK inhibition. The model confirms that phagocytosis-associated changes in the composition of the cell membrane can inhibit ERK activity and predicts that Akt and Ras-GAP synergize to inhibit ERK.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23133361/pdf/?tool=EBI |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rachel Leander Shipan Dai Larry S Schlesinger Avner Friedman |
spellingShingle |
Rachel Leander Shipan Dai Larry S Schlesinger Avner Friedman A mathematical model of CR3/TLR2 crosstalk in the context of Francisella tularensis infection. PLoS Computational Biology |
author_facet |
Rachel Leander Shipan Dai Larry S Schlesinger Avner Friedman |
author_sort |
Rachel Leander |
title |
A mathematical model of CR3/TLR2 crosstalk in the context of Francisella tularensis infection. |
title_short |
A mathematical model of CR3/TLR2 crosstalk in the context of Francisella tularensis infection. |
title_full |
A mathematical model of CR3/TLR2 crosstalk in the context of Francisella tularensis infection. |
title_fullStr |
A mathematical model of CR3/TLR2 crosstalk in the context of Francisella tularensis infection. |
title_full_unstemmed |
A mathematical model of CR3/TLR2 crosstalk in the context of Francisella tularensis infection. |
title_sort |
mathematical model of cr3/tlr2 crosstalk in the context of francisella tularensis infection. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Computational Biology |
issn |
1553-734X 1553-7358 |
publishDate |
2012-01-01 |
description |
Complement Receptor 3 (CR3) and Toll-like Receptor 2 (TLR2) are pattern recognition receptors expressed on the surface of human macrophages. Although these receptors are essential components for recognition by the innate immune system, pathogen coordinated crosstalk between them can suppress the production of protective cytokines and promote infection. Recognition of the virulent Schu S4 strain of the intracellular pathogen Francisella tularensis by host macrophages involves CR3/TLR2 crosstalk. Although experimental data provide evidence that Lyn kinase and PI3K are essential components of the CR3 pathway that influences TLR2 activity, additional responsible upstream signaling components remain unknown. In this paper we construct a mathematical model of CR3 and TLR2 signaling in response to F. tularensis. After demonstrating that the model is consistent with experimental results we perform numerical simulations to evaluate the contributions that Akt and Ras-GAP make to ERK inhibition. The model confirms that phagocytosis-associated changes in the composition of the cell membrane can inhibit ERK activity and predicts that Akt and Ras-GAP synergize to inhibit ERK. |
url |
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23133361/pdf/?tool=EBI |
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