A model of an integrated immune system pathway in Homo sapiens and its interaction with superantigen producing expression regulatory pathway in Staphylococcus aureus: comparing behavior of pathogen perturbed and unperturbed pathway.

Response of an immune system to a pathogen attack depends on the balance between the host immune defense and the virulence of the pathogen. Investigation of molecular interactions between the proteins of a host and a pathogen helps in identifying the pathogenic proteins. It is necessary to understan...

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Autores principales: Namrata Tomar, Rajat K De
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:f4836fbdf2cd42999db277ae160977bd2021-11-18T08:43:11ZA model of an integrated immune system pathway in Homo sapiens and its interaction with superantigen producing expression regulatory pathway in Staphylococcus aureus: comparing behavior of pathogen perturbed and unperturbed pathway.1932-620310.1371/journal.pone.0080918https://doaj.org/article/f4836fbdf2cd42999db277ae160977bd2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24324645/?tool=EBIhttps://doaj.org/toc/1932-6203Response of an immune system to a pathogen attack depends on the balance between the host immune defense and the virulence of the pathogen. Investigation of molecular interactions between the proteins of a host and a pathogen helps in identifying the pathogenic proteins. It is necessary to understand the dynamics of a normally behaved host system to evaluate the capacity of its immune system upon pathogen attack. In this study, we have compared the behavior of an unperturbed and pathogen perturbed host system. Moreover, we have developed a formalism under Flux Balance Analysis (FBA) for the optimization of conflicting objective functions. We have constructed an integrated pathway system, which includes Staphylococcal Superantigen (SAg) expression regulatory pathway and TCR signaling pathway of Homo sapiens. We have implemented the method on this pathway system and observed the behavior of host signaling molecules upon pathogen attack. The entire study has been divided into six different cases, based on the perturbed/unperturbed conditions. In other words, we have investigated unperturbed and pathogen perturbed human TCR signaling pathway, with different combinations of optimization of concentrations of regulatory and signaling molecules. One of these cases has aimed at finding out whether minimization of the toxin production in a pathogen leads to the change in the concentration levels of the proteins coded by TCR signaling pathway genes in the infected host. Based on the computed results, we have hypothesized that the balance between TCR signaling inhibitory and stimulatory molecules can keep TCR signaling system into resting/stimulating state, depending upon the perturbation. The proposed integrated host-pathogen interaction pathway model has accurately reflected the experimental evidences, which we have used for validation purpose. The significance of this kind of investigation lies in revealing the susceptible interaction points that can take back the Staphylococcal Enterotoxin (SE)-challenged system within the range of normal behavior.Namrata TomarRajat K DePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e80918 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Namrata Tomar
Rajat K De
A model of an integrated immune system pathway in Homo sapiens and its interaction with superantigen producing expression regulatory pathway in Staphylococcus aureus: comparing behavior of pathogen perturbed and unperturbed pathway.
description Response of an immune system to a pathogen attack depends on the balance between the host immune defense and the virulence of the pathogen. Investigation of molecular interactions between the proteins of a host and a pathogen helps in identifying the pathogenic proteins. It is necessary to understand the dynamics of a normally behaved host system to evaluate the capacity of its immune system upon pathogen attack. In this study, we have compared the behavior of an unperturbed and pathogen perturbed host system. Moreover, we have developed a formalism under Flux Balance Analysis (FBA) for the optimization of conflicting objective functions. We have constructed an integrated pathway system, which includes Staphylococcal Superantigen (SAg) expression regulatory pathway and TCR signaling pathway of Homo sapiens. We have implemented the method on this pathway system and observed the behavior of host signaling molecules upon pathogen attack. The entire study has been divided into six different cases, based on the perturbed/unperturbed conditions. In other words, we have investigated unperturbed and pathogen perturbed human TCR signaling pathway, with different combinations of optimization of concentrations of regulatory and signaling molecules. One of these cases has aimed at finding out whether minimization of the toxin production in a pathogen leads to the change in the concentration levels of the proteins coded by TCR signaling pathway genes in the infected host. Based on the computed results, we have hypothesized that the balance between TCR signaling inhibitory and stimulatory molecules can keep TCR signaling system into resting/stimulating state, depending upon the perturbation. The proposed integrated host-pathogen interaction pathway model has accurately reflected the experimental evidences, which we have used for validation purpose. The significance of this kind of investigation lies in revealing the susceptible interaction points that can take back the Staphylococcal Enterotoxin (SE)-challenged system within the range of normal behavior.
format article
author Namrata Tomar
Rajat K De
author_facet Namrata Tomar
Rajat K De
author_sort Namrata Tomar
title A model of an integrated immune system pathway in Homo sapiens and its interaction with superantigen producing expression regulatory pathway in Staphylococcus aureus: comparing behavior of pathogen perturbed and unperturbed pathway.
title_short A model of an integrated immune system pathway in Homo sapiens and its interaction with superantigen producing expression regulatory pathway in Staphylococcus aureus: comparing behavior of pathogen perturbed and unperturbed pathway.
title_full A model of an integrated immune system pathway in Homo sapiens and its interaction with superantigen producing expression regulatory pathway in Staphylococcus aureus: comparing behavior of pathogen perturbed and unperturbed pathway.
title_fullStr A model of an integrated immune system pathway in Homo sapiens and its interaction with superantigen producing expression regulatory pathway in Staphylococcus aureus: comparing behavior of pathogen perturbed and unperturbed pathway.
title_full_unstemmed A model of an integrated immune system pathway in Homo sapiens and its interaction with superantigen producing expression regulatory pathway in Staphylococcus aureus: comparing behavior of pathogen perturbed and unperturbed pathway.
title_sort model of an integrated immune system pathway in homo sapiens and its interaction with superantigen producing expression regulatory pathway in staphylococcus aureus: comparing behavior of pathogen perturbed and unperturbed pathway.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/f4836fbdf2cd42999db277ae160977bd
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