Many chronic inflammatory diseases are known to be caused by persistent bacterial or viral infections. A well-studied example is the tick-borne infection by the gram-negative spirochaetes of the genus Borrelia in humans and other mammals, causing severe symptoms of chronic inflammation and subsequent tissue damage (Lyme Disease), particularly in large joints and the central nervous system, but also in the heart and other tissues of untreated patients. Although killed efficiently by human phagocytic cells in vitro, Borrelia exhibits a remarkably high infectivity in mice and men. In experimentally infected mice, the first immune response almost clears the infection. However, approximately 1 week post infection, the bacterial population recovers and reaches an even larger size before entering the chronic phase. We developed a mathematical model describing the bacterial growth and the immune response against Borrelia burgdorferi in the C3H mouse strain that has been established as an experimental model for Lyme disease. The peculiar dynamics of the infection exclude two possible mechanistic explanations for the regrowth of the almost cleared bacteria. Neither the hypothesis of bacterial dissemination to different tissues nor a limitation of phagocytic capacity were compatible with experiment. The mathematical model predicts that Borrelia recovers from the strong initial immune response by the regrowth of an immune-resistant sub-population of the bacteria. The chronic phase appears as an equilibration of bacterial growth and adaptive immunity. This result has major implications for the development of the chronic phase of Borrelia infections as well as on potential protective clinical interventions.
Keywords: Borrelia burgdorferi, Lyme disease, mathematical model, immunology, macrophages, mouse model
Citation: Binder SC, Telschow A and Meyer-Hermann M (2012) Population dynamics of Borrelia burgdorferi in Lyme disease. Front. Microbio. 3:104. doi: 10.3389/fmicb.2012.00104
Received: 14 December 2011; Accepted: 01 March 2012;
Published online: 22 March 2012.
Edited by:Marc Thilo Figge, Leibniz-Institute for Natural Product Research and Infection Biology – Hans-Knoell-Institute, Germany
Reviewed by:Franziska Mech, Leibniz-Institute for Natural Product Research and Infection Biology – Hans-Knoell-Institute, Germany
Copyright: © 2012 Binder, Telschow and Meyer-Hermann. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
*Correspondence: Michael Meyer-Hermann, Department of Systems Immunology, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany. e-mail: email@example.com