John MacMicking PhD

Associate Professor of Microbial Pathogenesis

Research Interests

Cell-autonomous immunity; Constitutive and inducible host defense programs; Inflammasomes; Interferons (IFNs); Intracellular pathogens; Single cell analyses; Vertebrate and bacterial genetics


Research Summary

Our laboratory focuses on the biological question of how all nucleated cells - irrespective of tissue origin - protect themselves against infection. This broad-based system of non-classical host defense is called cell-autonomous immunity and has recently been studied in plants but remains poorly understood in higher vertebrates. We are interested in characterizing the antimicrobial genes and pathways which constitute the cell-autonomous defense network in mammals. Many of these genes including a new superfamily of immune GTPases are transcriptionally elicited via activating stimuli such as interferons (IFNs) and Toll-like receptor (TLR) signalling. The overall goal is to understand how individual cells protect themselves against major human bacterial pathogens like Mycobacterium tuberculosis and Salmonella serovars in vitro and in vivo. Some of the questions we are interested in are the following: What are the protein machineries and signaling hubs involved in restricting intracellular pathogens? Do such pathways operate in the cytosol or on specialized organelles, and is this response tailored to the subcellular lifestyle of the invading pathogen? Are common sets of host effectors shared across all diploid cells, or are there cell type-specific systems deployed in diverse histogenetic lineages and tissues? Lastly, can we reconstruct a virtual cell that assembles these host effector proteins and pathways in a coherent way? Answering these questions should help define the basic principles underlying this unique form of host resistance in complex, multicellular organisms.


Selected Publications

  • Randow F., MacMicking, J.D., and James, L.C. Cellular self-defense: How cell-autonomous immunity protects against pathogens. Science. 340,701-706 (2013).
  • Shenoy, A.R., Wellington, D.A., Kumar, P., Kassa, H., Booth, C.J., Cresswell, P., and MacMicking, J.D. GBP5 promotes NLRP3 inflammasome assembly and immunity in mammals. Science. 336, 481-485 (2012).
  • MacMicking, J.D. IFN-induced effector mechanisms in cell-autonomous immunity. Nature Reviews of Immunology. 12, 367-382. (2012).
  • Kim, B.H., Shenoy, A.R., Kumar, P., Bradfield, C.J., and MacMicking, J.D. IFN-inducible GTPases in host cell defense. Cell Host & Microbe. 12, 434-444 (2012).
  • Kim, B.H., Shenoy, A.R., Kumar, P., Das, R., Tiwari, S., and MacMicking, J.D. A family of IFN-gamma-inducible 65kD GTPases protect against bacterial infection. Science. 332, 717-721 (2011).
  • Tiwari, S., Choi, H.P., Matsuzawa, T., Pypaert, M, and MacMicking, J.D. Targeting of the GTPase Irgm1 to the phagosomal membrane via phosphatidylinositols PI(3,4)P2 and PI(3,4,5)P3 promotes immunity to mycobacteria. Nature Immunology. 10, 907-917 (2009).
  • MacMicking, J.D. Macrophage activation and host defense. Cell Host & Microbe. 5, 405-407 (2009).
  • Bougneres, L.#, Helft, J.#, Tiwari, S.#, Vargas, P., Chang, B.H.J., Chan, L., Campisi, L., Lauvau, G., Hugues, S., Kumar, P., Kamphorst, A.O., Lennonn Dumenil, A.M., Nussenzweig, M., MacMicking, J.D.#, Amigorina, S.#, and Guemonprez, P.# A role for lipid bodies in the cross-presentation of phagocytozed antigens by MHC class I in dendritic cells. Immunity. 3, 231-244 (2009). # Equally contributing
  • MacMicking, J.D. Immune control of phagosomal bacteria by p47 GTPases. Current. Opinion in Microbiology. 8,1-9 (2005).
  • MacMicking, J.D. IFN-inducible GTPases and immunity to intracellular pathogens. Trends Immunology. 25, 601-609 (2004).

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