B-Cell-Deficient Mice Show an Exacerbated Inflammatory Response in a Model of Chlamydophila abortus Infection

The resolution of Chlamydophila abortus (Chlamydia psittaci serotype 1) infection is dependent on gamma interferon and CD8(+) T cells, and classically, B cells have been considered to play a minimal role in host defense. The role of B cells in the immune response was studied by using a model of infection in mice with genetically modified immunoglobulin M transmembrane domains (μMT). In the absence of B cells, infection with C. abortus leads to an acute severe fatal disease that involves a disseminated intravascular coagulation syndrome. μMT mice displayed an increased level of proinflammatory cytokines in serum, and an increased number of neutrophils was observed in the lesions. The possible deleterious role of neutrophils in the pathogenesis of disease in μMT mice was determined by depletion of the neutrophils with the monoclonal antibody RB6-8C5. This led to an enhancement of the bacterial burden and early mortality in both μMT and wild-type mice, while necrotic lesions remained. Analysis of the presence of immunoregulatory cytokines showed significantly lower levels of transforming growth factor β in the sera of μMT mice. However, mice lacking mature B cells were able to establish a specific immune response that protected them from a secondary challenge. Taken together, these data suggest an immunomodulatory role for B cells in the early events of C. abortus primary infection that can protect mice against an exaggerated inflammatory response.

流产嗜衣原体（Chlamydophila abortus，鹦鹉热衣原体血清型1（Chlamydia psittaci serotype 1））感染的转归依赖于γ干扰素（gamma interferon）与CD8阳性T细胞，经典研究观点认为B细胞在宿主防御过程中仅发挥极小作用。本研究通过构建携带免疫球蛋白M跨膜结构域基因修饰的μMT小鼠感染模型，探究了B细胞在免疫应答中的功能。在缺乏B细胞的情况下，流产嗜衣原体感染会引发急性重症致死性疾病，伴随弥散性血管内凝血综合征（disseminated intravascular coagulation syndrome）。μMT小鼠的血清促炎细胞因子水平显著升高，病灶内中性粒细胞数量亦明显增加。本研究通过单克隆抗体RB6-8C5耗竭中性粒细胞，明确了中性粒细胞在μMT小鼠疾病发病机制中可能存在的有害作用。该干预手段会使μMT小鼠与野生型小鼠的细菌载量升高、早期死亡率上升，而坏死病灶仍持续存在。对免疫调节细胞因子的检测分析显示，μMT小鼠血清中的转化生长因子β（transforming growth factor β）水平显著降低。但缺乏成熟B细胞的小鼠仍可建立特异性免疫应答，使其免受二次感染攻击。综上，本研究数据表明，B细胞在流产嗜衣原体原发性感染的早期事件中发挥免疫调节作用，可保护小鼠免受过度炎症反应的损伤。