An Immunological Role in the CARDs

摘要

It's rare in this feature to highlight a researcher's work twice in the same year, because it is rare for a researcher to achieve what Gabriel Nunez's team at the University of Michigan, Ann Arbor, has accomplished. Besides generating at least three Hot Papers on NOD_1 and NOD_2 in a matter of a few months, Nunez helped create the discipline of intracellular pathogen recognition, and influenced the work of scientists in fields as diverse as genetics, innate and mucosal immunity, gastroenterology, and apoptosis research. Prior to publishing Hot Papers that connected NOD_2 mutations and Crohn disease, Nunez and others demonstrated that NOD_1 and NOD_2 (now officially known as CARD_4 and CARD_(15), respectively) play a role in innate immunity. In these two papers, Nunez's team published results arguing that CARD_4 and CARD_(25), both presumably cytosolic proteins, recognize the bacterial cell wall constituent lipopolysaccharide (IPS). Further, activating either protein stimulates the immunoregulatory transcription factor NF-κB. LPS recognition was initially criticized. And these results ultimately turned out to be based on contaminated reagents, proving the critics correct. Yet, it spurred further work and kept this group, as one researcher put it, "barking up the right tree."