Pathobiology of Lyme Disease Borrelia
Steven J. Norris, Jenifer Coburn, John M. Leong, Linden T. Hu and Magnus Höök
from: Borrelia: Molecular Biology, Host Interaction and Pathogenesis (Edited by: D. Scott Samuels and Justin D. Radolf). Caister Academic Press, U.K. (2010)
Lyme disease Borrelia are host-dependent, tick-transmitted, invasive, nontoxigenic, persistent pathogens that cause disease in humans and other mammals primarily through the induction of inflammatory reactions. During transmission from the infected tick, the bacteria undergo dramatic changes in gene expression, resulting in adaptation to the mammalian environment. Expression of outer surface protein C (OspC) is essential during these early stages of colonization, although the mechanism by which OspC promotes spirochetal infectivity is unknown. Organisms multiply and spread locally and induce an inflammatory response that in humans results in an erythema migrans, the hallmark lesion of localized infection. The spirochetes enter the bloodstream during the primary infection and colonize multiple tissue sites, leading to the disseminated stage of infection. Motility and chemotaxis mechanisms undoubtedly play a role in this process. Several borrelial proteins have been implicated in adherence to host cell surface proteins and extracellular matrix components and are likely to be involved in the homing of Borrelia to histologic compartments within each tissue, penetration of blood vessels and adherence to and migration through endothelial cells and tissue strata at distant sites. Activation of plasmin on the bacterial surface and induction of host proteases are thought to facilitate dissemination and/or inflammation. Most tissue damage appears to result from host inflammatory reactions. Although the mechanisms are not entirely understood, induction of cytokine/chemokine expression by bacterial lipoproteins and the resulting recruitment and activation of lymphocytes, macrophages and granulocytes play a major role in both local histopathology and constitutional symptoms. Despite their relatively low densities in tissues, Borrelia cause neurologic, cardiovascular, arthritic and dermatologic manifestations during the disseminated and persistent stages of infection by mechanisms that remain largely a mystery. Immune evasion mechanisms, including the vls antigenic variation system, complement-regulator acquiring surface proteins (CRASPs), down-regulation of highly antigenic surface proteins (such as OspC) and invasion of protective niches, permit the survival of the pathogens for months to years following infection despite robust antibody and cellular responses read more ...