The innate immune system of animals and plants has evolved to maintain a healthy "load" of endemic microorganisms. "Beneficial" commensals proliferate in various compartments of multicellular organisms;this is tolerated by the innate immune system. On the other hand, the innate immune system actively attempts (and, mostly succeeds) to suppress growth of harmful pathogens. Multiple signals from both host and microbe are integrated to produce an appropriate level of immunogenic response. Large gaps in our knowledge of the molecular and cellular coordination of pathogen response remain. The nematode Caenorhabditis elegans is a simple, genetically-tractable model host for the study of innate immunity. Recent work has demonstrated that the C. elegans protein CED-1, a homologue of mammalian scavenger receptors, regulates activation of the non-canonical unfolded protein response (UPR) during the host innate immune response. Moreover, it has been demonstrated that the nervous system, via the G-protein coupled receptor (GPCR) OCTR-1, controls CED-1-mediated immune responses. For this proposal, there are three specific Aims: 1) determine the spatial requirement for CED-1 activity during an innate immune response, 2) analysis of neural circuits that regulate innate immunity, and 3) characterization of pathways that regulate CED-1-dependent abu gene expression. This study will identify innate immune pathways upstream and downstream of OCTR-1/CED-1. This work will help in characterizing molecular pathways, cell autonomous and non-cell autonomous, that contribute to immunity to human pathogens and tolerance of microbial gut communities.

Public Health Relevance

The proposed research will investigate molecular and cellular pathways that control innate immunity in animals. Manipulation of these pathways may help to address current human health concerns related to multidrug resistant (MDR) bacteria, sepsis, autoimmune disorders, and chronic inflammatory diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM103122-02
Application #
8635214
Study Section
Special Emphasis Panel (ZRG1-F07-K (20))
Program Officer
Barski, Oleg
Project Start
2013-03-01
Project End
2015-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
2
Fiscal Year
2014
Total Cost
$55,094
Indirect Cost
Name
Duke University
Department
Genetics
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705