The University of Toledo

Associate Professor
Host/Pathogen Interactions in Lyme Disease
E-mail: R.Mark.Wooten@utoledo.edu 
Telephone: 419.383.6818
Fax:  419.383.3002

Education Director - Immunity & Infection
BSL3 Core Laboratory Director

link to read Mark's article on Lyme Disease ... 

Dr. Wooten's laboratory is interested in the host/pathogen interactions that lead to the development of two different infectious diseases: Lyme disease and melioidosis.

Lyme disease (i.e. Lyme arthritis) is a particularly interesting and complicated malady that involves two major events: 1) persistent infection of the host by the spirochete Borrelia burgdorferi and 2) the response of the host's innate immune defenses to the organism. B. burgdorferi is highly infectious tick-bourne spirochetal bacteria that is especially adept at evading host defenses and persisting in various tissues. The infected host mounts a vigorous immune response to these spirochetes, as evidenced by the production of large quantities of B. burgdorferi-specific antibodies. Although passive transfer of B. burgdorferi-specific antiserum can prevent infection of naive mice, the immune response elicited during natural infection is usually unable to clear the infection, resulting in a persisting bacterial reservoir that can re-emerge under various conditions. This persistence in target tissues promotes prolonged stimulation of the host's innate defenses via interaction with endogenous bacterial lipoproteins, resulting in activation of immune pathways that appear to mediate much of the inflammatory pathology indicative of Lyme disease. Based on these dynamics, we are interested in utilizing the well-established murine model of Lyme disease to address the following areas:

 - Identification of host immune cell types and mediators that are important in controlling the abilities of B. burgdorferi to infect, invade, and persist in mammalian host tissues.

 - Identification of host signaling pathways that modulate the inflammatory pathology that is characteristic for Lyme disease.

Melioidosis is a human and animal disease that is caused by infection with Burkholderia pseudomallei. Acute disease can involve fulminant septicemia with mortality rates of 40-90%, even with vigorous antibiotic and supportive therapy. Chronic disease can also develop, with recrudescence occurring months to years after initial exposure. Aerosolized B. pseudomallei has an LD50 <30 organisms in mice, thus giving it considerable potential for misuse as a biological weapon. There is currently no vaccine. Persistence within macrophages appears to be central to the development of melioidosis, enabling the bacteria to spread and evade humoral immunity. Very little is known about the molecular basis for B. pseudomallei virulence, but it appears that these bacteria suppress macrophage activity, preventing bacterial clearance and generation of an effective adaptive immune response. A better understanding of the basic biology of macrophage subversion by this bacterium would greatly facilitate the development of preventative and curative treatments. We are interested in utilizing the recently-developed murine model of melioidosis to address the following areas:

 - Identification of mechanisms that virulent B. pseudomallei strains utilize to circumvent efficient clearance by macrophages.

 - Identification of outer membrane proteins expressed by B. pseudomallei that might serve as virulence factors/vaccine candidates.

Dr. Wooten received his Masters in 1990 from the University of Arkansas (Fayetteville) under the supervision of Dr. Jim Saunders. He received his Ph.D. in 1995 from the University of Mississippi Medical Center under the supervision of Dr. Jan Bly. He completed post-doctoral training at the University of Utah College of Medicine in the laboratory of Dr. Janis Weis. Dr. Wooten joined the Department of Medical Microbiology and Immunology in May 2001.

Current grant funding:

-National Institutes of Health (R01) - Dysregulation of Innate Immune Responses by Borrelia burgdorferi: A Role for IL-10 (PI)

-The Dana Foundation (Program in Brain and Immuno-imaging) - Early interactions of Borrelia burgdorferi with immune cells resident in skin (PI)

-National Research Fund for Tick-Borne Diseases - Intravital assessment of interactions between Borrelia burgdorferi and immune cells in skin (PI)

-National Institutes of Health (U01) - Glanders Vaccine Development (co-PI)

-National Science Foundation (Biomedical Engineering, Research to Aid Persons with Disabilities, and Biophotonics Programs) - A new approach to regenerate   bone using microparticles seeded with mesenchymal stem cells and macrophages (co-Investigator) 

Representative Publications:

Woodman, M.E., Cooley, A.E., Avdiushko, R., Bowman, A., Botto, M., Wooten, R.M., van Rooijen, N., Cohen, D.A., Stevenson, B. (2009) Roles for phagocytic cells and complement in controlling relapsing fever infection.  J Leukoc Biol. 2009 Sep; 86(3):727-736.

Lazarus JJ, Kay MA, McCarter AL, Wooten RM. (2008) Viable Borrelia burgdorferi enhances interleukin-10 production and suppresses activation of murine macrophages. Infect Immun. Mar;76:1153-1162.

Lipski, S.L., Akimana, C., Timpe, J.M., Wooten, R.M., Lafontaine, E.R.  (2007)  The Moraxella catarrhalis autotransporter McaP is a conserved surface protein that mediates adherence to human epithelial cells through its N-terminal passenger domain.  Infect. Immun. 75:314-324.

Crandall, H., Dunn, D.M., Ma, Y., Wooten, R.M., Zachary, J.F., Weis, J.H., Weiss, R.B., Weiss, J.J.  (2006)  Gene expression profiling reveals unique pathways associated with differential severity of lyme arthritis.  J. Immunol. 177:7930-7942.

Lazarus, J.J., Meadows, M.J., Lintner, R.E., Wooten, R.M. (2006)  IL-10 Deficiency promotes increased Borrelia burgdorferi clearance predominantly through enhanced innate immune responses.  J Immunol. 177: 7076-7085.

Melillo, A., Sledjeski, D.D., Lipski, S., Wooten, R.M., Basrur, V., Lafontaine, E.R. (2006) Identification of aFrancisella tularensis LVS outer membrane protein that confers adherence to A549 human lung cells.  FEMS Microbiol. Lett. 263:102-108.

Lawrenz, M.B., Wooten, R.M., and Norris, S.T. (2004) Effects of vLsE Complementation on the Infectivity of Borrelia burgdorferi Lacking the Linear Plasmid Ip28-1. Infect. Immun., 72:6577-6585.

Lawrenz, M.B., Wooten, R.M., Zachary, J.F., Drouin, S.M., Weis, J.J., Wetsel, R.A., and Norris, S.J. (2003) Effect of Complement Component C3 Deficiency on Experimental Lyme Borreliosis in Mice. Infect. Immun., 71:4432-4440.

Yoder A., Wang X., Ma Y., Philipp, M. T., Heilbrun, M., Weis, J. H., Kirschning, C. J., Wooten, R. M., and Weis, J. J. (2003) Tripalmitoyl-S-Glyceryl-Cysteine-Dependent OspA Vaccination of Toll-Like Receptor 2-Deficient Mice Results in Effective Protection from Borrelia burgdorferi Challenge. Infect. Immun., 71:3894-3900.

Wooten, R. M., Ying, M. A., Yoder, R. A., Brown, J. P., Weis, J. H., Zachary, J. F., Kirschning, C. J., and Weis, J. J. (2002) Toll-like receptor 2 plays a pivotal role in host defense and inflammatory response to Borrelia burgdorferi. Vector Borne Zoonotic Dis, 2:275-278.

Wooten, R.M., Ma, Y., Yoder, R. A., Brown, J. P., Weis, J. H., Zachary, J. F., Kirschning, C. J., and Weis, J. J. (2002) Toll-like receptor 2 is required for innate, but not acquired, host defense to Borrelia burgdorferi. J. Immunol., 168:348-355.

Wooten, R. M. and Weis, J. J. (2001) Host-pathogen interactions promoting inflammatory Lyme arthritis: use of mouse models for dissection of disease processes. Curr. Opin. Micro., 4:274-279.

Brown, E. L., Wooten, R. M., Johnson, B. J., Iozzo, R. V., Smith, A., Dolan, M.C., Guo, B. P., Weis, J. J., and Hook, M. (2001) Resistance to Lyme disease in decorin-deficient mice. J. Clin. Invest., 107:845-852.

Brown, J. P., Zachary, J. F., Teuscher, C., Weis, J. J., and Wooten, R. M. (1999) Dual role of IL-10 in murine Lyme disease: Regulation of arthritis severity and host defense. Infect. Immun., 67:5142-5150.

Hirschfeld, M., Kirschning, C. J., Schwandner, R., Wesche, H., Weis, J. H., Wooten, R. M., and Weis, J. J. (1999) Cutting Edge: Inflammatory signaling by Borrelia burgdorferi lipoproteins is mediated by toll-like receptor 2. J. Immunol., 163:2382-2386.

Wooten, R. M., Morrison, T. B., Weis, J. H., Wright, S. D., Thieringer, R., and Weis, J. J. (1998) The role of CD14 in signaling mediated by outer membrane lipoproteins of Borrelia burgdorferi. J. Immunol., 160:5485-5492.

Wooten, R. M., Cutchens, M. A., Causey, A. L., Clem, L. W., and Bly, J. E. (1997) Effects of oleic acid on murine CD4+ T cell death and anti-CD3 or superantigen induced proliferation at low temperature. Dev. Comp. Immunol., 21:375-384.

Wooten, R. M., Modur, V. R., McIntyre, T. M., and Weis, J. J. (1996) Borrelia burgdorferi outer membrane protein A (OspA) induces nuclear translocation of NF-kB and inflammatory activation in human endothelial cells. J. Immunol., 157:4584-4590.

Causey, A. L., Wooten, R. M., Cuchen, M. A., Clem, L. W., and Bly, J. E. (1996) Anergy or cell death induced by low physiological temperature in mitogen-stimulated human T lymphocytes. J. Therm. Biology., 21:381-388.