Abstract
Cell-autonomous immunity operates across all three domains of life to defend the host from infection. This seminar will introduce some of guiding principles of cell-autonomous immunity and highlight the role played by new host defense proteins in orchestrating intracellular immunity to distinct pathogen classes. Many of these pathways are mobilized in response to signals from the interferon (IFN) family of cytokines as an evolutionary adaptation in higher species such as vertebrates. In particular, a new group of IFN-inducible GTPases will serve as an example of how cells defend their interior by tailoring antimicrobial activities according to the type of replicative niche that different pathogens occupy.
Biography
Dr. MacMicking studied organic chemistry and biochemistry (B.Sc, Hons 1) at the John Curtin School of Medical Research, Australian National University, in Canberra. He then undertook Ph.D studies with Carl Nathan in the combined Immunology program at Sloan-Kettering Institute-Cornell University Medical College in New York City before joining Rockefeller University as a Howard Hughes Medical Institute LSRF Fellow and Adjunct Assistant Professor. In 2004, he moved to Yale University where he is currently an HHMI Investigator, Member of the Yale Systems Biology Institute and tenured Associate Professor within the Departments of Microbial Pathogenesis and Immunobiology at Yale University School of Medicine.
Dr. MacMicking is best known for helping pioneer the field of cell-autonomous immunity. Over 20 years’ ago he generated some of the first genetic mutants to reveal a role for these cell-intrinsic host defense pathways, including the production of cytotoxic gases such as nitric oxide that are critical for resistance to infection. Between 1992-1995 he created the first knockout of an innate immune gene in mammals – inducible nitric oxide synthase (iNOS/NOS2) – that disclosed its widespread roles in cell-autonomous immunity against bacteria, viruses and protozoa. Thereafter he computationally identified, physically mapped and began biochemically characterizing a complete IFN-inducible GTPase superfamily comprising 47 loci across humans and mice at the Rockefeller University. This effort plus later studies at Yale have shown different immune GTPases direct antimicrobial host effector proteins to the pathogen vacuole or assemble protective responses in the cytosol, for example, the inflammasome machinery. For these discoveries he has received several awards, most recently being named an Investigator of the Howard Hughes Medical Institute in 2015.