Clearance of Citrobacter rodentium requires B cells but not secretory immunoglobulin A (IgA) or IgM antibodies
Clearance of Citrobacter rodentium requires B cells but not secretory immunoglobulin A (IgA) or IgM antibodies
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DOI：
10.1128/iai.72.6.3315-3324.2004
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发表时间：
2004-06-01
影响因子：
3.1
通讯作者：
Eckmann, L
中科院分区：
文献类型：
--
作者：
Maaser, C;Housley, MP;Eckmann, L
鼠柠檬酸杆菌是人类肠致病性大肠杆菌的小鼠模型病原体，主要在结肠和盲肠的管腔和粘膜表面定植，引起隐窝增生和粘膜炎症。小鼠感染C.齿龈会产生分泌性免疫球蛋白a （IgA）反应，但B细胞或分泌性抗体在宿主防御中的作用尚不清楚。为了解决这个问题，我们在缺乏B细胞、IgA、分泌IgM、聚合Ig受体（pIgR）或J链的小鼠中进行了口腔啮齿c感染。正常小鼠结肠和粪便细菌数量在1周时达到峰值，3 ~ 4周后细菌被根除。b细胞缺陷小鼠最初同样易感，但随后无法控制感染。组织反应有明显差异，正常小鼠感染后2周出现短暂的隐窝增生和结肠、盲肠黏膜炎症，而b细胞缺陷小鼠感染后2周黏膜变化不大，6周出现严重的上皮增生、溃疡和黏膜炎症。B细胞的功能不受分泌抗体的介导，因为缺乏IgA或分泌IgM或转运到管腔、pIgR或J链所需的蛋白质的小鼠，可以正常清除啮齿鼠。尽管如此，在正常和pigr缺陷小鼠中，全身注射免疫血清可显著减少细菌数量，而IgG的消耗则消除了这种作用。这些结果表明，宿主对啮齿鼠的防御依赖于B细胞和IgG抗体，而不需要产生或经上皮运输IgA或分泌的IgM。
Citrobacter rodentium, a murine model pathogen for human enteropathogenic Escherichia coli, predominantly colonizes the lumen and mucosal surface of the colon and cecum and causes crypt hyperplasia and mucosal inflammation. Mice infected with C. rodentium develop a secretory immunoglobulin A (IgA) response, but the role of B cells or secretory antibodies in host defense is unknown. To address this question, we conducted oral C. rodentium infections in mice lacking B cells, IgA, secreted IgM, polymeric Ig receptor (pIgR), or J chain. Normal mice showed peak bacterial numbers in colon and feces at 1 week and bacterial eradication after 3 to 4 weeks. B-cell-deficient mice were equally susceptible initially but could not control infection subsequently. Tissue responses showed marked differences, as infection of normal mice was accompanied by transient crypt hyperplasia and mucosal inflammation in the colon and cecum at 2 but not 6 weeks, whereas B-cell-deficient mice had few mucosal changes at 2 weeks but severe epithelial hyperplasia with ulcerations and mucosal inflammation at 6 weeks. The functions of B cells were not mediated by secretory antibodies, since mice lacking IgA or secreted IgM or proteins required for their transport into the lumen, pIgR or J chain, cleared C. rodentium normally. Nonetheless, systemic administration of immune sera reduced bacterial numbers significantly in normal and pIgR-deficient mice, and depletion of IgG abrogated this effect. These results indicate that host defense against C. rodentium depends on B cells and IgG antibodies but does not require production or transepithelial transport of IgA or secreted IgM.