Characteristics of Borrelia hermsii infection in human hematopoietic stem cell-engrafted mice mirror those of human relapsing fever.
Characteristics of Borrelia hermsii infection in human hematopoietic stem cell-engrafted mice mirror those of human relapsing fever.
复制标题
人类造血干细胞移植小鼠的赫氏疏螺旋体感染特征与人类回归热的特征相似。
DOI：
10.1073/pnas.1108776109
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发表时间：
2011
影响因子：
11.1
通讯作者：
Alugupalli,KishoreR
中科院分区：
文献类型：
--
作者：
Vuyyuru,Raja;Liu,Hongqi;Manser,Tim;Alugupalli,KishoreR
Rodents are natural reservoirs for a variety of species ofBorreliathat cause relapsing fever (RF) in humans. The murine model of this disease recapitulates many of the clinical manifestations of the human disease and has revealed that T cell-independent antibody responses are required to resolve the bacteremic episodes. However, it is not clear whether such protective humoral responses are mounted in humans. We examinedBorrelia hermsiiinfection in human hematopoietic stem cell-engrafted nonobese diabetic/SCID/IL-2Rγnullmice: “human immune system mice” (HISmice). Infection of these mice, which are severely deficient in lymphoid and myeloid compartments, withB. hermsiiresulted in persistent bacteremia. In contrast, this infection in HISmice resulted in recurrent episodes of bacteremia, the hallmark of RF. The resolution of the primary episode of bacteremia was concurrent with the generation ofB. hermsii-specific human IgM. Remarkably, HISmice generated antibody responses to theB. hermsiiouter-membrane protein Factor H binding protein A. Sera from humans infected byB. hermsiihave a similar reactivity, and studies in mice have shown that this response is generated by the B1b cell subset. HISmice contain several B-cell subsets, including those with the phenotype CD20+CD27+CD43+CD70−, a proposed human equivalent of mouse B1 cells. Reduction of B cells by administration of anti-human CD20 antibody resulted in diminished anti-B. hermsiiresponses and persistent bacteremia in HISmice. These data indicate that analysis ofB. hermsiiinfection in HISmice will serve as a model in which to study the cellular and molecular mechanisms involved in controlling human RF.
