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John D. MacMicking
Assistant Professor
Microbial Pathogenesis
Ph.D. Cornell University
(Sloan Kettering-Cornell Med)
New York, NY 1997
Visiting Assistant Professor
The Rockefeller University
New York, NY
email: john.macmicking@yale.edu
office: (203) 737-1570
lab: (203) 737-6707 |
Research Interests
Vertebrates have evolved complex innate immune response repertoires beyond
the primordial components found in lower multi-cellular organisms to combat
intracellular infections. The interferon (IFN) family represents one such
system, bridging both innate and acquired immunity as well as providing
direct protection in a cell-autonomous manner. Our group is identifiying
downstream IFN pathways that are crucial for controlling infection of
macrophages and dendritic cells by Mycobacterium tuberculosis
(Mtb), the causative agent of TB. Several IFN-inducible pathways
have recently been discovered, among them a group of GTPases that remodel
the phagosome of engulfed bacteria to restrict pathogen growth. We are
currently using a combination of mammalian and mycobacterial genetics along
with cell biology, immunology and protein crystallography to address the
mechanisms involved in these processes. In addition, a search for
Mtb components that combat IFN-induced host pathways is also
underway. These studies should lead to a better understanding of the
ancient dialogue between eukaryote and prokaryote while providing a basis
for rational TB vaccine or drug design in the future.
Selected References:
MacMicking, J.D., McKinney, J.D. (2004) Interaction of Mycobacterium tuberculosis with host macrophages. Curr. Opin. Microbiol. In press.
MacMicking, J.D. (2004) IFN-inducible GTPases and immunity to intracellular pathogens. Trends Immunol. In press.
Ng, V.H., Cox, J.S., Sousa, A.O., MacMicking, J.D., McKinney, J.D. (2004) Role of KatG catalase-peroxidase in mycobacterial pathogenesis: Countering the phagocyte oxidative burst. Mol. Microbiol. 52: 1291-1302.
MacMicking, J.D., Taylor, G.A., McKinney, J.D. (2003) Immune control of tuberculosis by interferon-γ-inducible LRG-47. Science 302: 654-659.
MacMicking J.D., McKinney, J.D. (2003) Macrophage immunity and Mycobacterium tuberculosis. In
Handbook of Experimental Pharmacology, Vol. 158: The Macrophage as Therapeutic Target.
Gordon, S. (ed). pp. 409-457
Shiloh, M.U., MacMicking, J.D., Nicholson, S., Brause, J.E., Potter, S., Marino, M., Fang, F.,
Dinauer, M., Nathan, C. (1999). Phenotype of mice and macrophages deficient in both phagocyte
oxidase and inducible nitric oxide synthase. Immunity 10: 29-38.
Karupiah, G., Mahalingam, S., Chen, J.H., Nathan, C.F., MacMicking, J.D. (1998). Rapid IFN-γ-dependent clearance of influenza A virus and protection from consolidating pneumonitis in nitric oxide synthase 2-deficient mice. J. Exp. Med. 188: 1541-1546
Diefenbach, A., Schindler, H., Donhauser, N., Lorenz, E., Laskay, T., MacMicking, J., Röllinghoff, M., Gresser, I., Bogdan, C. (1998). Type 1 interferon (IFN-α/β) and type 2 nitric oxide synthase regulate the innate immune response to a protozoan parasite. Immunity 8: 77-87.
MacMicking, J., Xie, Q.-w., Nathan, C. (1997). Nitric oxide and macrophage function. Ann. Rev. Immunol. 15: 323-350.
MacMicking, J.D., North, R.J., LaCourse, R., Mudgett, J.S., Shah, S.K., Nathan, C.F. (1997). Identification of nitric oxide synthase as a protective locus against tuberculosis. Proc. Natl Acad. Sci. USA. 94: 5243-5248.
MacMicking, J.D., Nathan, C., Hom, G., Chartrain, N., Trumbauer, M., Stevens, K., Xie, Q.-w., Sokol, K., Fletcher, D.S., Hutchinson, N., Chen, H., Mudgett, J.S. (1995). Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase. Cell 81: 641-650.
Karupiah, G., Xie, Q.-w., Buller, R.M.L., Nathan, C., Duarte, C., MacMicking, J.D. (1993). Inhibition of viral replication by interferon-γ-induced nitric oxide synthase. Science 261: 1445-1448.
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