Protein NLRP7 serves as a scout in macrophage or white blood cells, detects and eliminates bacterial cell wall components in harmful gram-positive bacteria such as Staphylococcus aureus and Listeria monocytogenes. The findings will be published in the February 23 issue of the journal Immunity.
"NLRP7 is a novel intracellular pattern recognition receptor that specifically recognizes bacterial cell wall components, known as lipopeptides, in harmful bacteria," says Stehlik, who worked closely with collaborators Andrea Dorfleutner, research assistant professor of medicine at Feinberg, and Yon Rojanasakul, Robert C. Byrd Distinguished Professor and Benedum Distinguished Professor at West Virgina University. "We show that activation of NLRP7 is necessary for eradicating bacterial infections through the formation of protein complexes called inflammasomes, which enable the production of defense factors in immune cells."
Identifying the molecule was complicated, says Sonal Khare, postdoctoral fellow at Feinberg and first author on the research paper, because the family of proteins within macrophages is quite large. "There were 22 likely candidates. To determine which one of these proteins is able to recognize bacteria in macrophages, we had to remove each one of them," she says. Through process of elimination, the team identified NLRP7 as the required protein.
Understanding how the immune system recognizes these deadly intruders could one day lead to novel treatment strategies to combat these infections.
"The next phase of research related to NLRP7 and inflammasomes is progressing," says Stehlik. "We are continuing the research to explore mechanisms behind how this NLRP7 inflammasome is formed. We want to know whether we can manipulate this process to make the response stronger. We also will be exploring the use of mouse models in this pathway to study this response in vivo."