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B细胞在宿主抵御原发性伯氏考克斯氏体感染中的作用。

Role of B cells in host defense against primary Coxiella burnetii infection.

作者信息

Schoenlaub Laura, Elliott Alexandra, Freches Danielle, Mitchell William J, Zhang Guoquan

机构信息

Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, Missouri, USA.

Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, Missouri, USA

出版信息

Infect Immun. 2015 Dec;83(12):4826-36. doi: 10.1128/IAI.01073-15. Epub 2015 Oct 5.

Abstract

Despite Coxiella burnetii being an obligate intracellular bacterial pathogen, our recent study demonstrated that B cells play a critical role in vaccine-induced immunity to C. burnetii infection by producing protective antibodies. However, the role of B cells in host defense against primary C. burnetii infection remains unclear. In this study, we investigated whether B cells play an important role in host defense against primary C. burnetii infection. The results showed that peritoneal B cells were able to phagocytose virulent C. burnetii bacteria and form Coxiella-containing vacuoles (CCVs) and that C. burnetii can infect and replicate in peritoneal B1a subset B cells in vitro, demonstrating a potential role for peritoneal B cells in host defense against C. burnetii infection in vivo. In addition, the results showing that B1a cells secreted a high level of interleukin-10 (IL-10) in response to C. burnetii infection in vitro suggest that B1a cells may play an important role in inhibiting the C. burnetii infection-induced inflammatory response. The observation that adoptive transfer of peritoneal B cells did not significantly affect the severity of C. burnetii infection-induced diseases in both severe combined immunity-deficient (SCID) and μMT mice indicates that peritoneal B cells alone may not be able to control C. burnetii infection. In contrast, our finding that C. burnetii infection induced more-severe splenomegaly and a higher bacterial burden in the spleens of B1a cell-deficient Bruton's tyrosine kinase x-linked immunity-deficient (BTK(xid)) mice than in their wild-type counterparts further suggests that B1a cells play an important role in host defense against primary C. burnetii infection.

摘要

尽管伯氏考克斯体是一种专性细胞内细菌病原体,但我们最近的研究表明,B细胞通过产生保护性抗体在疫苗诱导的针对伯氏考克斯体感染的免疫中发挥关键作用。然而,B细胞在宿主抵御原发性伯氏考克斯体感染中的作用仍不清楚。在本研究中,我们调查了B细胞在宿主抵御原发性伯氏考克斯体感染中是否发挥重要作用。结果显示,腹膜B细胞能够吞噬毒力强的伯氏考克斯体细菌并形成含考克斯体的液泡(CCV),并且伯氏考克斯体能够在体外感染腹膜B1a亚群B细胞并在其中复制,这表明腹膜B细胞在宿主抵御体内伯氏考克斯体感染中具有潜在作用。此外,体外实验结果显示B1a细胞在受到伯氏考克斯体感染时会分泌高水平的白细胞介素-10(IL-10),这表明B1a细胞可能在抑制伯氏考克斯体感染诱导的炎症反应中发挥重要作用。在严重联合免疫缺陷(SCID)小鼠和μMT小鼠中,腹膜B细胞的过继转移对伯氏考克斯体感染诱导疾病的严重程度没有显著影响,这表明仅腹膜B细胞可能无法控制伯氏考克斯体感染。相比之下,我们发现,与野生型对照小鼠相比,在B1a细胞缺陷的布鲁顿酪氨酸激酶X连锁免疫缺陷(BTK(xid))小鼠中,伯氏考克斯体感染诱导了更严重的脾肿大和脾脏中更高的细菌载量,这进一步表明B1a细胞在宿主抵御原发性伯氏考克斯体感染中发挥重要作用。

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