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Abstract
Lyme disease is the most common vector-borne disease in the United States and Europe, caused by a tick-borne spirochete, Borrelia burgdorferi. Life cycle alternation between arthropod and mammals enhanced B. burgdorferi to adapt to two diverse niches. Although B. burgdorferi infection in these reservoir hosts appears asymptomatic, infection in human can typically cause inflammation in the skin, nervous system, musculoskeletal system and heart. In this review, we discuss the basic molecular characteristics and cell biology of B. burgdorferi and provide an overview of spirochete-induced activation of innate and adaptive immunity, resulting in particular immunopathology. Advancing understanding of the immune evasion mechanisms of B. burgdorferi provides important implications for ongoing research and clinical practice of Lyme disease.
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Figure 1.
Life cycle of Borrelia burgdorferi. Ixodes ticks have three life stages that require blood: larvae, nymphs, and adults. Because B. burgdorferi is not vertically transmitted by ticks to their offspring, larvae become infected when feeding on infected reservoir animals and transmit the infection to new animals during their next bloodmeal. Nymphal ticks appear to be responsible for the majority of human transmission in the eastern U.S.; the majority of human cases occur in late spring and summer when this stage is most commonly encountered. Many mammals and birds have been implicated as reservoirs for B. burgdorferi in the U.S., although in most of the sites where transmission is intense, white-footed mice appear to most frequently contribute to the spirochetal life cycle (3).
Figure 2.
Innate and adaptive immune activation in response to B. burgdorferi infection. B. burgdorferi are initially recognized by innate immune effector cells such as dendritic cells (DCs), neutrophils and macrophages; activation of these cells increases following internalization and degradation of spirochetes within phagolysosomes. DCs that have taken up spirochetes migrate to the lymph nodes, where they present processed B. burgdorferi antigens to T cells and B cells. While T cells enter the circulation and are recruited to the site of infection, B cells can be differentiated into plasma cells that can secrete specific antibodies that can kill B. burgdorferi via complement-dependent and -independent pathways. Production of pro-inflammatory cytokines by activated macrophages results in the recruitment of additional neutrophils, T cells, macrophages and DCs to the bite site, and eventually the development of erythema migrans (3).
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