A Keck Medicine of USC-led team of microbiologists has identified previously unknown interactions between critical proteins in the human immune response system, uncovering two independent regulatory mechanisms that keep the body's immune response in check. Their findings appear in the February 2014 edition of the journal Cell Host & Microbe.
"The body's response to infection consists of a complex network of biological processes set off by the intrusion of disease-causing microbes," says Qiming Liang, PhD, a USC post-doctoral fellow and study co-author. "This is a powerful response that needs precise regulation to ensure that the host body is not harmed after the pathogen is destroyed."
For this reason, the authors suggest that it is just as important to know what stops the body's immune response as what activates it. Scientists do not yet fully understand this regulatory mechanism and continue to study it in hopes of harnessing its power to cure disease.
"We report that the direct interaction between the cGAS DNA sensor and the Beclin-1 autophagy protein shapes innate immune responses by regulating both the production of the cGAMP molecule and the process that destructs the microbial DNA," says Gil Ju Seo, PhD, a post-doctoral fellow and study co-author. "This is significant because the cGAMP molecule signals the production of inflammatory cytokines, which kill viruses and bacteria but can also harm the body if uncontrolled."
Led by Jae U. Jung, PhD, professor and chair of the Department of Molecular Microbiology and Immunology at the Keck School of Medicine of USC, the research team collaborated with the University of Illinois at Urbana-Champaign, Howard Hughes Medical Institute, Korea Advanced Institute of Science and Technology in Korea, and Ludwig-Maximilians University in Germany. Other Keck Medicine of USC authors include Youn Jung Choi, Ph.D. candidate; Jianning Ge, Ph.D.; Mary A. Rodgers, Ph.D.; and Mude Shi, Ph.D., all of whom are part of Jung's lab. Their work was supported by grants from the National Institutes of Health (1F32AI096698, CA82057, CA31363, CA115284, CA180779, DE023926, AI105809, AI073099, HL110609, AI083025), Hastings Foundation, Fletcher Jones Foundation, Howard Hughes Medical Institute, and the GRL Program (K20815000001) from the National Research Foundation of Korea.