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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Autores principales:	Rachel Leander, Shipan Dai, Larry S Schlesinger, Avner Friedman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/66547be67da0495b9c21c01f3ec8d6cb
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spelling	oai:doaj.org-article:66547be67da0495b9c21c01f3ec8d6cb2021-11-18T05:52:44ZA mathematical model of CR3/TLR2 crosstalk in the context of Francisella tularensis infection.1553-734X1553-735810.1371/journal.pcbi.1002757https://doaj.org/article/66547be67da0495b9c21c01f3ec8d6cb2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23133361/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Complement 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.Rachel LeanderShipan DaiLarry S SchlesingerAvner FriedmanPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 8, Iss 11, p e1002757 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Rachel Leander Shipan Dai Larry S Schlesinger Avner Friedman A mathematical model of CR3/TLR2 crosstalk in the context of Francisella tularensis infection.
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.
format	article
author	Rachel Leander Shipan Dai Larry S Schlesinger Avner Friedman
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)
publishDate	2012
url	https://doaj.org/article/66547be67da0495b9c21c01f3ec8d6cb
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A mathematical model of CR3/TLR2 crosstalk in the context of Francisella tularensis infection.

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