Abstract
Many pathogens make use of antigenic variation as a way to evade the host immune response. A key mechanism for immune evasion and persistent infection by the Lyme disease spirochete, Borrelia burgdorferi, is antigenic variation of the VlsE surface protein. Recombination results in changes in the VlsE surface protein that prevent recognition by VlsE-specific antibodies in the infected host. Despite the presence of a substantial number of additional proteins residing on the bacterial surface, VlsE is the only known antigen that exhibits ongoing variation of its surface epitopes. This suggests that B. burgdorferi may utilize a VlsE-mediated system for immune avoidance of its surface antigens. To address this, the requirement of VlsE for host reinfection by the Lyme disease pathogen was investigated. Host-adapted wild type and VlsE mutant spirochetes were used to reinfect immunocompetent mice that had naturally cleared an infection with a VlsE-deficient clone. Our results demonstrate that variable VlsE is necessary for reinfection by B. burgdorferi, and this ability is directly related to evasion of the host antibody response. Moreover, the data presented here raise the possibility that VlsE prevents recognition of B. burgdorferi surface antigens from host antibodies. Overall, our findings represent a significant advance in our knowledge of immune evasion by B. burgdorferi, and provide insight to the possible mechanisms involved in VlsE-mediated immune avoidance.
Highlights
Borrelia burgdorferi is the causative agent of the multisystem disease known as Lyme borreliosis, which is currently the most prevalent vector-borne disease in North America [1,2,3]
The inherent problem with these experiments is that in vitrocultured B. burgdorferi were utilized, which have been shown to have a 32-fold reduction in VlsE expression levels relative to those measured during murine infection [35]
The difference in the ability of B. burgdorferi clones to reinfect does not seem to be attributed to any noticeable difference in the total Borrelia-specific antibody response. These results suggest that the immune response of these mice to non-VlsE surface antigens can sufficiently block reinfection by a B. burgdorferi clone lacking VlsE, but is unable to prevent reinfection by the wild type (WT) clone containing VlsE
Summary
Borrelia burgdorferi is the causative agent of the multisystem disease known as Lyme borreliosis, which is currently the most prevalent vector-borne disease in North America [1,2,3] Infection with this spirochete can be severely debilitating to both animals and humans, resulting in long-term manifestations including arthritis, carditis, and neurological problems [4]. Clones lacking lp were shown to exhibit an intermediate infectivity phenotype whereby these spirochetes were able to disseminate to tissue sites but were unable to persist in the murine host These same clones are capable of long-term survival in severe-combined immunodeficient (SCID) mice that lack an effective antibody response [21,22]. Spirochetes that lack only the vls locus due to telomere-mediated removal are completely cleared from immunocompetent C3H mice by 21 days post infection [24], confirming the hypothesis that vls recombination functions to evade the humoral immune response in the mouse host [14,16,25,26]
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