Host-Pathogen Coupled Interactions
Abstract
Understanding the complex interactions of pathogens and host macrophages during the initial stage of infection (generally the first 12-48 hours) will help identify key targets for potential therapeutic interventions and provide information to optimize both drug treatment timing and dosing characteristics. As a pathogen moves from the external environment into the host, the pathogen is endocytosed by host immune cells, and in the course of infection can escape back into the tissue or bloodstream of the host. During this process the pathogen responds to time-varying environmental triggers by activating and modulating its own signaling pathways so as to produce appropriate responses that facilitate its survival. Many of these responses modulate host pathways and thereby alter the pathogen's environment. In this way multiple interacting feedback loops are set up between the pathogen and its host. The current proposal aims to understand these interacting pathways and develop quantitative predictive models of both host cell and pathogen behavior during the initial course of intracellular pathogen infection, so as to elucidate signaling mechanisms elicited and within Francisella tularensis (FT), Yersinia pestis (YP) and others (Burkholderia mallei and/or B. pseudomallei) during infection, particularly in response to specific environmental conditions occurring within host compartments, as well as interactions between these signaling networks in bacteria and those within host responder cells (e.g., macrophages), and their combined effect on the host's overall (immune) response.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 04, 2015
- Accession Number
- ADA620250
Entities
People
- C. E. Hack
- Jeffery M. Gearhart
- Peter J. Robinson
Organizations
- Air Force Research Laboratory