NYMC Faculty Publications

Controlling the Outcome of the Toll-Like Receptor Signaling Pathways

Author Type(s)

Faculty

Additional Author Affiliation

Touro College of Dental Medicine at NYMC

DOI

10.1371/journal.pone.0031341

Journal Title

PLoS One

First Page

31341

Last Page

31341

Document Type

Article

Publication Date

1-1-2012

Department

Pharmacology

Abstract

The Toll-Like Receptors (TLRs) are proteins involved in the immune system that increase cytokine levels when triggered. While cytokines coordinate the response to infection, they appear to be detrimental to the host when reaching too high levels. Several studies have shown that the deletion of specific TLRs was beneficial for the host, as cytokine levels were decreased consequently. It is not clear, however, how targeting other components of the TLR pathways can improve the responses to infections. We applied the concept of Minimal Cut Sets (MCS) to the ihsTLR v1.0 model of the TLR pathways to determine sets of reactions whose knockouts disrupt these pathways. We decomposed the TLR network into 34 modules and determined signatures for each MCS, i.e. the list of targeted modules. We uncovered 2,669 MCS organized in 68 signatures. Very few MCS targeted directly the TLRs, indicating that they may not be efficient targets for controlling these pathways. We mapped the species of the TLR network to genes in human and mouse, and determined more than 10,000 Essential Gene Sets (EGS). Each EGS provides genes whose deletion suppresses the network's outputs.

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