The human intestinal microbiome includes viruses that replicate in eukaryotic cells, plants, fungi or bacteria. However, very little is known on how viral recognition shapes mucosal immune responses. Furthermore, a detailed understanding of the signaling intermediates that confer the sensing of viruses for induction of type I interferons s critical for strategies to curtail viral mechanisms that impede innate immune defenses. Our work identified the guanine nucleotide exchange factor H1 (GEF-H1), encoded by the arhgef2 gene, as a central component of host defense activation during viral infections. We hypothesize that GEF-H1 serves as a gatekeeper for innate host defenses by controlling interferon response factor activation, which is part of signaling pathways induced by recognition of bacteria and viruses. Defining the functional role of this newly discovered central component of microbial pattern recognition should provide pivotal insights into the integration of antiviral host defenses into immune activation pathways that control the microbiota in the intestine.

Public Health Relevance

A detailed understanding of sensing of microbial components for the induction of host defenses is critical for strategies to curtail microbial mechanisms that disable immune responses or induce chronic inflammation. We aim to unravel the mechanisms that make GEF-H1 a central signaling component that controls the expression of type I interferons and proinflammatory mediators for the defense against viral and bacterial infections.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
1R01AI113333-01
Application #
8766256
Study Section
Immunity and Host Defense (IHD)
Program Officer
Rothermel, Annette L
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199