Probing Gene Regulatory Networks to Decipher Host–Pathogen Interactions.

Abstract

Given the pivotal role that macrophages play in determining the outcome of infection, it is now becoming apparent that a better understanding of the molecular interplay between the pathogen and this host cell type will be crucial for developing more effective strategies for tuberculosis therapy. In this context the need to capture the dynamic features of this crosstalk, so as to dissect the evolving stages of host–pathogen equilibration, is also beginning to be appreciated. A promising way to probe the ongoing dialog between the macrophage and the pathogen is through gene expression profiling. An analysis of the gene expression pattern of the infected host cell on the one hand, and that of the infecting pathogen on the other, provides a coarse grained insight into the nature and dynamics of interactions between these two entities. While much more work needs to be done in this direction, initial studies are beginning to shed light on the mechanisms by which the pathogen equilibrates within the host intracellular environment. However, an important goal here would be to extract the gene regulatory networks that emerge within the pathogen and the host cell, and to then precisely map the interface between these two networks. In addition to yielding important information on crosstalk mechanisms, such mapping should also help to identify novel targets for drug development.