A Mathematical Model of the Dynamics of Cytokine Expression and Human Immune Cell Activation in Response to the Pathogen Staphylococcus aureus

Cell-based mathematical models have previously been developed to simulate the immune system in response to pathogens. Mathematical modeling papers which study the human immune response to pathogens have predicted concentrations of a variety of cells, including activated and resting macrophages, plas...

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Autores principales:	Kian Talaei, Steven A. Garan, Barbara de Melo Quintela, Mette S. Olufsen, Joshua Cho, Julia R. Jahansooz, Puneet K. Bhullar, Elliott K. Suen, Walter J. Piszker, Nuno R. B. Martins, Matheus Avila Moreira de Paula, Rodrigo Weber dos Santos, Marcelo Lobosco
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	cytokines mathematical modeling immune response immune system Staphycoccus aureus cytokine response Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e5739fc564e3458c8d31f09fe87aec56
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spelling	oai:doaj.org-article:e5739fc564e3458c8d31f09fe87aec562021-11-12T10:51:59ZA Mathematical Model of the Dynamics of Cytokine Expression and Human Immune Cell Activation in Response to the Pathogen Staphylococcus aureus2235-298810.3389/fcimb.2021.711153https://doaj.org/article/e5739fc564e3458c8d31f09fe87aec562021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcimb.2021.711153/fullhttps://doaj.org/toc/2235-2988Cell-based mathematical models have previously been developed to simulate the immune system in response to pathogens. Mathematical modeling papers which study the human immune response to pathogens have predicted concentrations of a variety of cells, including activated and resting macrophages, plasma cells, and antibodies. This study aims to create a comprehensive mathematical model that can predict cytokine levels in response to a gram-positive bacterium, S. aureus by coupling previous models. To accomplish this, the cytokines Tumor Necrosis Factor Alpha (TNF-α), Interleukin 6 (IL-6), Interleukin 8 (IL-8), and Interleukin 10 (IL-10) are included to quantify the relationship between cytokine release from macrophages and the concentration of the pathogen, S. aureus, ex vivo. Partial differential equations (PDEs) are used to model cellular response and ordinary differential equations (ODEs) are used to model cytokine response, and interactions between both components produce a more robust and more complete systems-level understanding of immune activation. In the coupled cellular and cytokine model outlined in this paper, a low concentration of S. aureus is used to stimulate the measured cellular response and cytokine expression. Results show that our cellular activation and cytokine expression model characterizing septic conditions can predict ex vivo mechanisms in response to gram-negative and gram-positive bacteria. Our simulations provide new insights into how the human immune system responds to infections from different pathogens. Novel applications of these insights help in the development of more powerful tools and protocols in infection biology.Kian TalaeiKian TalaeiKian TalaeiSteven A. GaranSteven A. GaranBarbara de Melo QuintelaMette S. OlufsenJoshua ChoJoshua ChoJoshua ChoJulia R. JahansoozJulia R. JahansoozPuneet K. BhullarPuneet K. BhullarElliott K. SuenElliott K. SuenWalter J. PiszkerWalter J. PiszkerNuno R. B. MartinsMatheus Avila Moreira de PaulaRodrigo Weber dos SantosMarcelo LoboscoFrontiers Media S.A.articlecytokinesmathematical modelingimmune responseimmune systemStaphycoccus aureuscytokine responseMicrobiologyQR1-502ENFrontiers in Cellular and Infection Microbiology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cytokines mathematical modeling immune response immune system Staphycoccus aureus cytokine response Microbiology QR1-502
spellingShingle	cytokines mathematical modeling immune response immune system Staphycoccus aureus cytokine response Microbiology QR1-502 Kian Talaei Kian Talaei Kian Talaei Steven A. Garan Steven A. Garan Barbara de Melo Quintela Mette S. Olufsen Joshua Cho Joshua Cho Joshua Cho Julia R. Jahansooz Julia R. Jahansooz Puneet K. Bhullar Puneet K. Bhullar Elliott K. Suen Elliott K. Suen Walter J. Piszker Walter J. Piszker Nuno R. B. Martins Matheus Avila Moreira de Paula Rodrigo Weber dos Santos Marcelo Lobosco A Mathematical Model of the Dynamics of Cytokine Expression and Human Immune Cell Activation in Response to the Pathogen Staphylococcus aureus
description	Cell-based mathematical models have previously been developed to simulate the immune system in response to pathogens. Mathematical modeling papers which study the human immune response to pathogens have predicted concentrations of a variety of cells, including activated and resting macrophages, plasma cells, and antibodies. This study aims to create a comprehensive mathematical model that can predict cytokine levels in response to a gram-positive bacterium, S. aureus by coupling previous models. To accomplish this, the cytokines Tumor Necrosis Factor Alpha (TNF-α), Interleukin 6 (IL-6), Interleukin 8 (IL-8), and Interleukin 10 (IL-10) are included to quantify the relationship between cytokine release from macrophages and the concentration of the pathogen, S. aureus, ex vivo. Partial differential equations (PDEs) are used to model cellular response and ordinary differential equations (ODEs) are used to model cytokine response, and interactions between both components produce a more robust and more complete systems-level understanding of immune activation. In the coupled cellular and cytokine model outlined in this paper, a low concentration of S. aureus is used to stimulate the measured cellular response and cytokine expression. Results show that our cellular activation and cytokine expression model characterizing septic conditions can predict ex vivo mechanisms in response to gram-negative and gram-positive bacteria. Our simulations provide new insights into how the human immune system responds to infections from different pathogens. Novel applications of these insights help in the development of more powerful tools and protocols in infection biology.
format	article
author	Kian Talaei Kian Talaei Kian Talaei Steven A. Garan Steven A. Garan Barbara de Melo Quintela Mette S. Olufsen Joshua Cho Joshua Cho Joshua Cho Julia R. Jahansooz Julia R. Jahansooz Puneet K. Bhullar Puneet K. Bhullar Elliott K. Suen Elliott K. Suen Walter J. Piszker Walter J. Piszker Nuno R. B. Martins Matheus Avila Moreira de Paula Rodrigo Weber dos Santos Marcelo Lobosco
author_facet	Kian Talaei Kian Talaei Kian Talaei Steven A. Garan Steven A. Garan Barbara de Melo Quintela Mette S. Olufsen Joshua Cho Joshua Cho Joshua Cho Julia R. Jahansooz Julia R. Jahansooz Puneet K. Bhullar Puneet K. Bhullar Elliott K. Suen Elliott K. Suen Walter J. Piszker Walter J. Piszker Nuno R. B. Martins Matheus Avila Moreira de Paula Rodrigo Weber dos Santos Marcelo Lobosco
author_sort	Kian Talaei
title	A Mathematical Model of the Dynamics of Cytokine Expression and Human Immune Cell Activation in Response to the Pathogen Staphylococcus aureus
title_short	A Mathematical Model of the Dynamics of Cytokine Expression and Human Immune Cell Activation in Response to the Pathogen Staphylococcus aureus
title_full	A Mathematical Model of the Dynamics of Cytokine Expression and Human Immune Cell Activation in Response to the Pathogen Staphylococcus aureus
title_fullStr	A Mathematical Model of the Dynamics of Cytokine Expression and Human Immune Cell Activation in Response to the Pathogen Staphylococcus aureus
title_full_unstemmed	A Mathematical Model of the Dynamics of Cytokine Expression and Human Immune Cell Activation in Response to the Pathogen Staphylococcus aureus
title_sort	mathematical model of the dynamics of cytokine expression and human immune cell activation in response to the pathogen staphylococcus aureus
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/e5739fc564e3458c8d31f09fe87aec56
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A Mathematical Model of the Dynamics of Cytokine Expression and Human Immune Cell Activation in Response to the Pathogen Staphylococcus aureus

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