Pattern recognition receptors sense pathogen-associated molecular patterns and mediate the earliest host innate immune response to infection. The cytosolic nucleotide oligomerization domain (NOD) like receptors (NLRs) are a highly conserved group of cytosolic proteins that play a central role in the immune response to diverse microorganisms, environmental insults and cellular danger signals. We have recently demonstrated a role for Nlrp6 in the control of enteric virus infection. Nlrp6 controls enteric virus infection in the intestine by interacting with a RNA sensor, Dhx15. Here we propose to define the mechanisms of NLRP6-mediated anti-viral pathways, to identify whether other helicases may also interact with NLRP6 (Aim 1), whether other relevant RNA viruses are recognized through this pathway, and whether mutations may underlie certain human cases of vaccine failures (Aim 2). A fuller understanding of the triggers and physiologic function and signaling pathways for NLRs will provide key insights to immune mechanisms involved in host defense and immune-mediated diseases.
We have recently demonstrated that NLRP6, one of a highly conserved group of cytosolic proteins that play a central role in the immune response, plays an important role in the control of intestinal viral infections. Here we propose to identify other interacting viral sensors and other viruses for which this pathway provides a therapeutic target.