“Background Lyme disease, caused by tick-borne Borrelia

“Background Lyme disease, caused by tick-borne Borrelia

burgdorferi, is a multi-systemic and multi-phasic disease in humans, which includes pauciarticular arthritis in up to 60% of untreated patients [1, 2]. In the absence of antibiotic treatment, arthritis and other lesions undergo resolution with variable bouts of recurrence over the course of months to years of persistent infection [3]. Laboratory mice develop arthritis and carditis that follow a similar multi-phasic course as humans, with resolution and periodic bouts of recurrence over the course of persistent infection [4]. The mouse model has implicated the humoral immune response as a critical factor in arthritis and carditis resolution. Infection of Evofosfamide T-cell deficient (Tcr α/βnull, Tcr γ/δ-null), but not B-cell deficient (Igh6-null) or severe combined immunodeficient (SCID) or Rag1-null mice follows a course of resolution that is similar to fully immunocompetent mice [5], and passive transfer of serum from actively infected immunocompetent mice that have undergone DNA/RNA Synthesis inhibitor disease resolution (immune serum) into infected SCID mice results in complete resolution of arthritis and carditis, but

not clearance of infection [6–8]. Identification of the B. burgdorferi antigens targeted by antibodies that mediate disease resolution is complicated by the fact that B. burgdorferi grown in culture medium does not reflect the antigenic profile of spirochetes this website during mammalian infection [9, 10]. As a means to identify vulnerable antigenic targets that are expressed in the mammalian host that are responsible for antibody-mediated disease resolution, immune serum from actively infected mice has been used to probe B. burgdorferi genomic expression libraries or outer membrane extracts. These efforts revealed arthritis-related protein (BBF01/Arp) as well as decorin binding protein A (DbpA), among other antigens expressed during infection [8, 11–13]. Antiserum generated in mice hyperimmunized

with non-lipidated recombinant Arp or DbpA induced arthritis and carditis resolution, but did not eliminate infection, when passively transferred (-)-p-Bromotetramisole Oxalate to actively infected SCID mice [8, 12]. Immunization with DbpA was found to induce protective immunity against cultured spirochetes [11, 14], but not tick-borne spirochetes [15], whereas Arp immunization was ineffective at eliciting protective immunity against cultured spirochetes [16]. Outer surface protein C (OspC), another immunogenic protein expressed during infection, has also been shown to be vulnerable to passively transferred OspC antibody in SCID mice, but is down-regulated in response to specific antibody, thereby avoiding immune clearance in immunocompetent mice [17, 18].

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