Michele S. Swanson

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University of Michigan
Medical School
Microbiology & Immunology
ProfessorAppointed: 2008
Professional Headshot of Michele S. Swanson

Mailing Address

Microbiology and Immunology
6734 Med Sci II
University of Michigan Medical Center
Ann Arbor, Michigan 48109-5620
United States

Contact Information

Phone: (734) 647-7295
Fax: (734) 764-3562
mswanson@umich.edu

Qualifications

Ph.D., Harvard University, Genetics, 1991.
M.S., Columbia University, Genetics, 1986.
B.S., Yale University, Biology, 1982.

Expertise and Research Interests

Innate and adaptive immune responses are initiated when macrophages ingest microbes. To investigate the mechanisms that govern the outcome of this encounter, we exploit a bacterial pathogen as a genetic probe of macrophage function. Legionella pneumophila is an opportunistic human pathogen whose natural reservoir is fresh water amoebae. When inhaled, the gram-negative bacteria can colonize alveolar macrophages and cause the severe pneumonia, Legionnaires' disease.

Metabolic cues govern virulence expression:
To persist in the environment, L. pneumophila alternates between distinct cell types. A replicative cell grows within vacuoles of amoebae and macrophages, and a motile and resilient transmissive form is equipped to escape a spent host and primed to invade a naive one. By applying genetic, biochemical and cell biological methods, we have identified a variety of metabolic cues that govern the pathogen's lifecycle. To resume replication, intracellular L. pneumophila rely on Phagosomal transporter proteins to obtain essential metabolites and the bacterial enzyme SpoT to degrade the alarmone guanosine tetraphosphate (ppGpp). Once the intracellular progeny have exhausted the local nutrient supply, ppGpp accumulates and cooperates with other regulatory proteins to coordinate bacterial expression of transmissive traits, including cytotoxicity, motility, stress resistance, and the capacity to block phagosome-lysosome fusion. By coupling cellular differentiation to its metabolic state, L. pneumophila swiftly acclimates to stresses encountered in its host or the environment, thereby enhancing its overall fitness.

Autophagy and pyroptosis, two barriers to infection:
Although L. pneumophila can replicate in human macrophages and fresh water amoebae, mice are naturally resistant to infection. Accordingly, our laboratory exploits a mouse infection model to investigate how the host innate immune system can detect and respond to infection by intracellular pathogens. Genetic analysis of human Crohn's disease, the plant response to tobacco mosaic virus, and mouse restriction of L. pneumophila infection each indicate that cells coordinately regulate autophagy and programmed cell death to combat infection. Accordingly, we are applying bacterial and mouse genetics and cell biological methods to test the hypothesis that, in response to cytosolic contamination with flagellin or other microbial products, NOD-like receptor proteins equip mouse macrophages either to induce autophagy to degrade intracellular microbes or to undergo pyroptosis, a failsafe caspase-1-dependent pro-inflammatory cell death.

Other Expertise

Councilor, Society for Leukocyte Biology (2006-09)
Chair, American Society for Microbiology, Microbial Pathogenesis Division B (2009)
Vice-Chair/Chair, FASEB Summer Research Conference, "Microbial Pathogenesis: Mechanisms of Infectious Disease" (2007-09)
Editor, Molecular Biology and Microbiology Reviews (2006-)
Editorial Board, Infection and Immunity (2001-06); Autophagy (2005-); Molecular Microbiology (2008-); Journal of Leukocyte Biology (2009-)
Waxman Foundation for Microbiology Lecture Program (2004-06)
President's Advisory Commission on Women's Issues, University of Michigan (2006-)
Board Member, Women's Intercollegiate Sports Endowment & Resource, Yale University (2005-)
Ad hoc Reviewer, Journals
Molecular Microbiology, Cellular Microbiology, Microbial Pathogenesis, Trends in Microbiology, Microbiology, Journal of Bacteriology, Current Biology, Proceedings of the National Academy Science, Nature, Nature Reviews Microbiology, Science, Journal of Experimental Medicine, Journal of Virology
Ad hoc Reviewer, Grant Agencies
North Carolina Biotechnology Center, National Science Foundation, University of Michigan Biomedical Research Council, Wellcome Trust
Ad hoc Member, NIH Study Sections
2001-National Institutes of Health, NIAID Bacteriology and Mycology-2
2001-National Institutes of Health, NIAID Special Emphasis Panel
"Ecology of Infectious Diseases"
2003-National Institutes of Health, NIAID Bacteriology and Mycology-1
2006-National Institutes of Health, NIAID, Host Interactions with Bacterial Pathogens
2008-National Institutes of Health, NIAID, Regional Centers for Excellence, Emerging Infectious Diseases Research Program

Keywords

COS Keywords:

Bacteria, Biofilms, Cell Biology, Immunology, Macrophage, Microbial Pathogenesis, Microbiology, Parasitology, Pathogenesis.

Additional Terms:

Autophagy, Bacterial Metabolism, Legionella pneumophila, Legionnaires Disease, Macrophage Lysosomes, Microbial Pathogenesis, Pathogens.

Memberships

American Society for Cell Biology
American Society for Microbiology
Society for Leukocyte Biology

Honors and Awards

2009, Division D Lecturer, American Society for Microbiology
2007, Faculty Recognition Award, University of Michigan
2003-2004, Elizabeth Caroline Crosby Award, National Science Foundation ADVANCE Project, University of Michigan
1997-2002, Presidential Early Career Award for Scientists and Engineers, The National Science and Technology Council, Washington DC

Previous Positions

2003-2004, Visiting Professor, Pasteur Institute, Genetics of Biofilms Laboratory
2002-2008, Associate Professor, University of Michigan, Medical School, Microbiology & Immunology
1996-2002, Assistant Professor, University of Michigan, Medical School, Microbiology & Immunology
1992-1996, American Cancer Society Postdoctoral Research Fellow, Tufts University, Medical School

Funding Received

  • U.S. HHS National Institutes of Health: Evasion of Macrophage Lysosomes by Legionella pneumophila, UM ID# 03-1428, 7/01/2003 to 12/31/2007.
  • U.S. HHS National Institutes of Health: Analysis of Legionella pneumophila Virulence Regulation, UM ID# 99-1266, 6/1/99 to 5/31/04.
  • National Institutes of Health (NIH): Autophagy as a Component of the Macrophage Innate Immune Response to L. pneumophila, 2008 to 2010.
  • U.S. HHS National Institutes of Health: Evasion of Macrophage Lysosomes by Legionella pneumophila, UM ID# 96-1979, 12/1/96 to 11/30/01.
  • Health and Human Services, Department of-National Institutes of Health: The Role of Legionella Pneumophilia Surface Properties in Lysosomal Evasion, UM ID# 04-1905, 09/01/2004 to 08/31/2008.
  • Health and Human Services, Department of-National Institutes of Health: Analysis of L. Pneumophila Virulence Regulation, UM ID# 05-3683, 02/15/2006 to 01/31/2011.

Publications

  • Yeung T, Heit B, Dubuisson JF, Fairn GD, Chiu B, Inman R, Kapus A, Swanson M, Grinstein S (Jun 2009) Contribution of phosphatidylserine to membrane surface charge and protein targeting during phagosome maturation., Journal of Cell Biology, 185 (5), 917-28 Abstract
  • Edwards RL, Dalebroux ZD, Swanson MS (Mar 2009) Legionella pneumophila couples fatty acid flux to microbial differentiation and virulence., Molecular Microbiology, 71 (5), 1190-1204 Abstract
  • Dalebroux ZD, Edwards RL, Swanson MS (Feb 2009) SpoT governs Legionella pneumophila differentiation in host macrophages., Molecular Microbiology, 71 (3), 640-58 Abstract
  • Swanson MS, Byrne BG, Dubuisson JF (2009) Kinetic analysis of autophagosome formation and turnover in primary mouse macrophages., Methods in Enzymology, 452, 383-402 Abstract
  • Whitfield, N, Byrne, B, Swanson, M (2009) Mouse macrophages are permissive to motile Legionella species that fail to trigger pyroptosis, Infect Immun, In Press
  • Chen DE, Podell S, Sauer JD, Swanson MS, Saier MH (Jan 2008) The phagosomal nutrient transporter (Pht) family., Microbiology (Reading, England), 154 (Pt 1), 42-53 Abstract
  • Klionsky DJ, Et Al (2008) Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes., Autophagy, 4 (2), 151-75 Abstract
  • Swanson MS (Oct 2006) Autophagy: eating for good health., Journal of Immunology (Baltimore, Md. : 1950), 177 (8), 4945-51 Abstract
  • Fernandez-Moreira E, Helbig JH, Swanson MS (Jun 2006) Membrane vesicles shed by Legionella pneumophila inhibit fusion of phagosomes with lysosomes., Infection and Immunity, 74 (6), 3285-95 Abstract
  • Molofsky AB, Byrne BG, Whitfield NN, Madigan CA, Fuse ET, Tateda K, Swanson MS (Apr 2006) Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection., Journal of Experimental Medicine, 203 (4), 1093-104 Abstract
  • Dubuisson JF, Swanson MS (2006) Mouse infection by Legionella, a model to analyze autophagy., Autophagy, 2 (3), 179-82 Abstract
  • Molofsky AB, Shetron-Rama LM, Swanson MS (Sep 2005) Components of the Legionella pneumophila flagellar regulon contribute to multiple virulence traits, including lysosome avoidance and macrophage death., Infection and Immunity, 73 (9), 5720-34 Abstract
  • Sauer JD, Shannon JG, Howe D, Hayes SF, Swanson MS, Heinzen RA (Aug 2005) Specificity of Legionella pneumophila and Coxiella burnetii vacuoles and versatility of Legionella pneumophila revealed by coinfection., Infection and Immunity, 73 (8), 4494-504 Abstract
  • Sauer JD, Bachman MA, Swanson MS (Jul 2005) The phagosomal transporter A couples threonine acquisition to differentiation and replication of Legionella pneumophila in macrophages., Proceedings of the National Academy of Sciences of the United States of America., 102 (28), 9924-9 Abstract
  • Amer AO, Swanson MS (Jun 2005) Autophagy is an immediate macrophage response to Legionella pneumophila., Cellular Microbiology, 7 (6), 765-78 Abstract
  • Amer AO, Byrne BG, Swanson MS (Apr 2005) Macrophages rapidly transfer pathogens from lipid raft vacuoles to autophagosomes., Autophagy, 1 (1), 53-8 Abstract
  • Swanson MS, Molofsky AB (2005) Autophagy and inflammatory cell death, partners of innate immunity., Autophagy, 1 (3), 174-6 Abstract
  • Molofsky AB, Swanson MS, Differentiate to thrive: lessons from the Legionella pneumophila life cycle, Molecular Microbiology, 53(1), 29-40, Jul 2004 Abstract
  • Bachman MA, Swanson MS, The LetE protein enhances expression of multiple LetA/LetS-dependent transmission traits by Legionella pneumophila, Infection and Immunity, 72(6), 3284-93, 2004 Abstract
  • Bachman MA, Swanson MS, Genetic evidence that Legionella pneumophila RpoS modulates expression of the transmission phenotype in both the exponential phase and the stationary phase, Infection and Immunity, 72(5), 2468-76, 2004 Abstract
  • Molofsky AB, Swanson MS, Legionella pneumophila CsrA is a pivotal repressor of transmission traits and activator of replication, Molecular Microbiology, 50(2), 445-61, October 2003 Abstract
  • Bandyopadhyay P, Byrne B, Chan Y, Swanson MS, Steinman HM, Legionella pneumophila catalase-peroxidases are required for proper trafficking and growth in primary macrophages, Infection and Immunity, 71(8), 4526-35, August 2003 Abstract
  • Hammer BK, Tateda ES, Swanson MS, A two-component regulator induces the transmission phenotype of stationary-phase Legionella pneumophila, Molecular Microbiology, 44(1), 107-18, April 2002 Abstract
  • Swanson MS, Fernandez-Moreira E, A microbial strategy to multiply in macrophages: the pregnant pause, Traffic, 3(3), 170-7, March 2002 Abstract
  • Amer AO, Swanson MS, A phagosome of one's own: a microbial guide to life in the macrophage, Current Opinion in Microbiology, 5(1), 56-61, February 2002 Abstract
  • Bachman MA, Swanson MS, RpoS co-operates with other factors to induce Legionella pneumophila virulence in the stationary phase, Molecular Microbiology, 40(5), 1201-14, June 2001 Abstract
  • Tateda K, Moore TA, Deng JC, Newstead MW, Zeng X, Matsukawa A, Swanson MS, Yamaguchi K, Standiford TJ, Early recruitment of neutrophils determines subsequent T1/T2 host responses in a murine model of Legionella pneumophila pneumonia, Journal of Immunology, 166(5), 3355-61, March 2001 Abstract
  • Joshi AD, Sturgill-Koszycki S, Swanson MS, Evidence that Dot-dependent and -independent factors isolate the Legionella pneumophila phagosome from the endocytic network in mouse macrophages, Cellular Microbiology, 3(2), 99-114, February 2001 Abstract
  • Sturgill-Koszycki S, Swanson MS, Legionella pneumophila replication vacuoles mature into acidic, endocytic organelles, Journal of Experimental Medicine, 192(9), 1261-72, November 2000 Abstract
  • Swanson MS, Sturgill-Koszycki I, Exploitation of macrophages as a replication niche by Legionella pneumophila, Trends in Microbiology, 8(2), 47-9, 2000 Abstract
  • Swanson MS, Hammer BK, Legionella pneumophila pathogesesis: a fateful journey from amoebae to macrophages, Annual Review of Microbiology, 54, 567-613, 2000 Abstract
  • Joshi AD, Swanson MS, Comparative analysis of Legionella pneumophila and Legionella micdadei virulence traits, Infection and Immunity, 67(8), 4134-42, August 1999 Abstract
  • Hammer BK, Swanson MS, Co-ordination of legionella pneumophila virulence with entry into stationary phase by ppGpp, Molecular Microbiology, 33(4), 721-31, 1999 Abstract
  • Byrne B, Swanson MS, Expression of Legionella pneumophila virulence traits in response to growth conditions, Infection and Immunity, 66(7), 3029-34, 1998 Abstract
  • Swanson MS, Isberg RR, Analysis of the intracellular fate of Legionella pneumophila mutants, Annals of the New York Academy of Sciences, 797, 8-18, 1996 Abstract
  • Swanson MS, Isberg RR, Identification of Legionella pneumophila mutants that have aberrant intracellular fates, Infection and Immunity, 64(7), 2585-94, 1996 Abstract
  • Swanson MS, Isberg RR, Association of Legionella pneumophila with the macrophage endoplasmic reticulum, Infection and Immunity, 63(9), 3609-20, 1995 Abstract
  • Dietrich WF, Damron DM, Isberg RR, Lander ES, Swanson MS, Lgn1, a gene that determines susceptibility to Legionella pneumophila, maps to mouse chromosome 13, Genomics, 26(3), 443-50, 1995 Abstract

Profile Details

Last Verified: 10/12/2009

COS Expertise ID #419864
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