MOLECULAR MECHANISMS GOVERNING HOST–MICROBE INTERACTION NETWORKS

Abstract

Host-microbe interactions are vital in physiological homeostasis, immunological responses as well as disease development. Nevertheless, the molecular pathways underlying these interactions are poorly understood and are still in pieces due to individual pathway studies. The purpose of this study is to examine in a systematic manner the co-ordinated molecular networks which mediate host-microbe communication using a pathway- and network-based analysis tool. A systematic literature-based and database-guided methodology was used in which pathway mapping was done using KEGG and Reactome as well as gene ontology-based functional annotation was done to build host and microbe interaction networks. The analysis involved key signaling pathways, such as Toll-like receptor (TLR), nuclear factor kappa B (NF-kB) and mitogen-activated protein kinase (MAPK) and microbial regulatory mechanisms, such as quorum sensing and metabolite-mediated signaling. The findings indicate that these routes intersect at key regulatory nodes, with very dynamic networks that integrate immune response, inflammation and cellular plasticity. Additionally, network-level measures bring into focus the contribution of the feedback loops and cross-pathway interactions to homeostasis and dysregulation in disease conditions. This systems-level framework offers insight into the processes of hostbased microbe interaction and outlines a set of potential molecular targets to act on in the context of a microbiome-associated disease. The results will fill the gap in the molecular signaling and network biology of host-microbe systems.