How the Neutrophil Both Kills and Protects the Lyme Spirochete, Borrelia Burgdorferi
Ruth Montgomery, Ph.D.
Senior Research Scientist
S-413, The Anlyan Center
My research focuses on the functions of phagocytic cells, both macrophages and neutrophils, and their interaction with the Lyme disease spirochete, Borrelia burgdorferi. We are exploring the paradox of spirochete persistence in vivo despite rapid and efficient killing by phagocytes in vitro. Our comprehensive examination of phagocyte killing mechanisms using confocal microscopy and quantitative biochemical and molecular methods has shown that despite the failure of immune clearance, there does not appear to be a global impairment of macrophage function in the infected host. Indeed, there is site-specific activation of macrophages, and no evidence of pressure toward downregulation of inflammatory activity.
In the early innate immune response, before the development of specific immunity, antibody is critical for clearance of B. burgdorferi by PMN, and significant killing of spirochetes by PMN occurs extracellularly. Many PMN components are effective against B. burgdorferi, including granule contents and the PMN’s abundant cytosolic protein, calprotectin. Vector saliva is a potent immune modulator and we have shown one mechanism for its inhibition of PMN function is down-regulation of leukocyte integrins. In our ongoing work, we are addressing critical questions of phagocyte function and pathogenesis in Lyme disease.
Selected Recent Publications
- Montgomery, R. R., Nathanson, M. H. and Malawista, S. E. 1993. The fate of Borrelia burgdorferi, the agent for Lyme disease, in mouse macrophages: Destruction, survival, recovery. J. Immunol.150:909-915.
- Montgomery, R. R., X.-M. Wang, and S. E. Malawista. 2001. Murine Lyme disease: No evidence for active immune downregulation in resolving or subclinical infection. J. Infect. Dis., 183: 1631-7.
- Lusitani D, Malawista SE, Montgomery RR. Borrelia burgdorferi are susceptible to killing by a variety of PMN components. J. Infect. Dis. 2002;185:797-804.
- Montgomery, R.R., Lusitani, D.L., de Boisfleury Chevance, A., and Malawista, S.E. 2002. Human phagocytic cells in the early innate immune response to Borrelia burgdorferi. J. Infect. Dis. 185:1773-1779.
- Lusitani, D.L., Malawista, S.E., and Montgomery, R.R. 2003. Calprotectin, an abundant cytosolic protein from human polymorphonuclear leukocytes, inhibits the growth of Borrelia burgdorferi. Infect. Immun. 71:4711-4716.
- Montgomery, R. R. 2003. Now they eat them, now they don’t: Phagocytes and Borrelia burgdorferi in Lyme disease. Microbiol. Today 30:165-6.
- Montgomery, R. R., D. Lusitani, A. de Boisfleury Chevance, and S. E. Malawista. 2004. Tick Saliva Reduces Adherence and Area of Human Neutrophils. Infect. Immun. in press.