Immunopathogenesis of Lyme borreliosis

Abstract

The clinical entity known as Lyme disease or Lyme borreliosis is caused by infection with Borrelia burgdorferi (and other recently described Borrelia species, whose differences from B. burgdorferi are currently being defined). It is, however, far from clear how this organism causes multisystem inflammatory damage. 1 Recent studies suggest that persistence of the organism may be implicated in chronic tissue damage, for example, chronic cardiomyopathy. 2–4 In the absence of toxin formation or invasive behavior by the organism, 5 the search for pathogenetic mechanisms has focused on the immunologic reactivity elicited by B. burgdorferi; of note is the fact that in severe combined immune deficiency (scid) mice, tissue damage develops even in the absence of an intact immune system. 6 This article is a review of the in vitro and in vivo immunologic responses to B. burgdorferi that have been identified and speculation about how these may then cause tissue damage or dysfunction. It deals with three questions: 1. 1. What immunologic responses does B. burgdorferi elicit in human or animal hosts? 2. 2. What in B. burgdorferi elicits these changes? 3. 3. How might these changes elicit tissue damage/cause disease? The ability of B. burgdorferi to elicit antigen-specific and nonspecific responses has been reviewed previously. 7,8 Antigen-specific T-cell 9,10 and humoral 11 reactivities have been used for diagnostic purposes. The immunologic changes elicited by B. burgdorferi are summarized by broad category in Table 1. These mechanisms, activated by live or dead organisms, can then cause chronic inflammation and tissue damage (Table 2) in a number of ways, summarized in this review. It has been suggested that specific immune responses may be implicated in the pathogenesis of certain aspects of the disease. Recent studies have shown differences in antigenic properties of North American and European strains of B. burgdorferi and suggested that these differences might be related to the different clinical features of Lyme disease (borreliosis) on the two continents. 12,13 Worthy of mention, however, is the fact that nonimmune mechanisms may be active in the pathogenesis of tissue dysfunction in Lyme disease; a recent fascinating study documents that a degradation component of tryptophan, produced by lipopolysaccharide-induced mononuclear cells, can diffuse across the blood-brain barrier and cause brain dysfunction (encephalopathy) in the absence of inflammation (encephalitis). Thus, patients may have brain dysfunction without having a central nervous system Borrelia infection. 14