Does the brain differentially alter metabolic and immunologic programs in the bone marrow in a pathogen-specific manner?
EMSL Project ID
60142
Abstract
: A wide variety of pathogens present an acute survival challenge in humans, and our ability to rapidly and precisely respond to these pathogens is critical to our survival as a species. Although there are some common immune responses to different classes of pathogens (e.g. viruses, bacteria, etc.), effective control and elimination of pathogens requires rapid deployment of immune resources directed specifically at the invading pathogen class. The central nervous system (CNS) is a critical site of sensing and bioamplification of immune signals from invading pathogens. This function is critical in producing behavioral, metabolic, and immunologic adaptations in a pathogen-specific manner to enhance survival. For example, recent data demonstrate that glucose intake is protective during viral infection but lethal during bacterial inflammation, whereas ketogenic metabolism (fasting) is protective during bacterial infection but detrimental during viral inflammation. In addition to CNS-mediated behavioral and metabolic responses to acute infection, it is clear that the autonomic nervous system (ANS) in the periphery is a major modulator of immune responses by exerting both pro and anti-inflammatory functions through influence on immune effector cells. Specifically, in the bone marrow, the ANS regulates immune stem cell niche homeostasis, immune cell regeneration, and fine-tunes the inflammatory response. Given that centers in the CNS exert powerful control over ANS function, we hypothesize that the CNS plays a key role in recognition of acute infections, and directs rapid peripheral (marrow and spleen) immune responses that are specific to pathogen class (viral, bacterial, etc.). This implies that the CNS is a key integrative site that ensures synergistic cooperation of behavioral, metabolic, and immune programs designed to meet pathogen challenges.This project will use an integrative approach of combining multi-omics (metabolomics, lipidomics and transcriptomics) and immunological data – leveraging unique capabilities and expertise at PNNL and OHSU- to obtain a systems-level mechanistic understanding of how the brain differentially modulates peripheral metabolism by sensing bacterial or viral infection.
Project Details
Start Date
2021-06-05
End Date
2023-10-01
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members