Transfer of immune serum from immunocompetent mice infected with B. burgdorferi protects mice against syringe challenge, and transfer of immune serum after infection is established induces arthritis resolution but does not clear infection or spirochetemia or resolve carditis. Immune serum had very-high-titer passive protective activity against syringe challenge but failed to protect mice against host-adapted spirochetes when they were challenged with infected tissue transplants. Mice were passively immunized at selected intervals relative to challenge inoculation with antisera to recombinant forms of an immunodominant region of flagellin, P39, and OspC (which are recognized by immune serum), but none provided protection or modified existing infection or disease. Results suggest that spirochetes within joints, but not in other tissues, are selectively vulnerable to immune serum and that immune serum appears to contain antibody against yet-to-be-identified antigens that may be selectively expressed in the context of joint tissue.
SummaryThe outer surface proteins (Osps) of Borrelia burgdotferi, the etiologic agent of Lyme disease, are principle targets of protective immune responses against this organism. Whereas most North American strains of B. burgdotferi in culture express an abundant amount of Osp A, antibodies to this protein are either absent or only weakly detected in the sera of naturally infected patients or experimentally infected mice. In contrast, Osp C, which has variable expression on cultured organisms, elicits an early, strong humoral response. To examine this paradox, we have studied the in vivo adaptation of a cloned population of B. burgdotferi strain N40 during the early course of experimental murine borreliosis. As in human disease, antibodies to Osp A were only weakly present in the early immune repertoire after murine inoculation with low dose (103) spirochetes. In contrast, antibodies to Osp C were prominent, even though on cultured spirochetes Osp C mRNA and protein expression could not be detected by reverse transcription polymerase chain reaction (RT-PCR) or indirect immunofluorescence, respectively. These observations led us to investigate the expression ofOsp A and Osp C in vivo. By direct fluorescent staining of uncultured spirochetes ex vivo and by PCR amplification of spirochetal mRNA, we show that Osp C is indeed expressed by some spirochetes after infection in the mouse. Spirochetes expressing Osp A could also be detected within the first 2 wk of infection, but not at 30 d. Osp A mRNA, although present at day 14 of infection, could not be amplified by RT-PCR at day 30, suggesting that the expression of this Osp is transient. This further implies that the late burst in Osp A antibodies in both mice and humans may be anamnestic. These results indicate that either Osp C is upregulated on spirochetes after infection, or Osp C-expressing spirochetes expand preferentially over those expressing Osp A during infection. These results have important implications for vaccine design and offer one explanation for the failure of Osp A antibodies to eradicate spirochetes from the infected host.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.