How the innate immune system discriminates pathogen attack from colonization with harmless commensal microbes is a fundamental unresolved question. One model suggests that the host responds to endogenous ligands generated as a consequence of the tissue damage associated with infection (DAMPs) and that these ligands must be encountered alongside the better-characterized Microbial-Associated Molecular Patterns (MAMPs) to induce a robust inflammatory response. Another possibility is suggested by our recent discovery that host proteins, which have undergone very specific post-translational modifications due to the activity of microbial-derived effectors or toxins, may themselves trigger an innate immune response. These Virulence-effector Associated Molecular Patterns (VAMPs) are distinct from DAMPs in that they are not simply due to cytotoxicity but instead occur specifically after exposure to virulent pathogens that actively target host proteins.Importantly, VAMPs can be generated early in the course of infection and can induce strong and potentially protective immune responses. We refer to these as 'effector-triggered' immune (ETI) responses. Here we propose studies to identify and better understand bacterial effectors that generate VAMPs and induce ETI.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
7R01GM102482-02
Application #
8810271
Study Section
Innate Immunity and Inflammation Study Section (III)
Program Officer
Dunsmore, Sarah
Project Start
2013-04-01
Project End
2017-02-28
Budget Start
2013-08-01
Budget End
2014-02-28
Support Year
Fiscal Year
2013
Total Cost
$242,907
Indirect Cost
$100,856
Name
Benaroya Research Institute at Virginia Mason
Department
Type
DUNS #
076647908
City
Seattle
State
WA
Country
United States
Zip Code
98101