Department für Infektiologie, Medizinische Mikrobiologie und Hygiene, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany.
Infect Immun. 2011 Jan;79(1):220-8. doi: 10.1128/IAI.00565-10. Epub 2010 Oct 18.
Pasteurella multocida is a Gram-negative bacillus that infects a number of wild and domestic animals, causing respiratory diseases. Toxigenic Pasteurella multocida strains produce a protein toxin (PMT) that leads to atrophic rhinitis in swine due to enhanced osteoclastogenesis and the inhibition of osteoblast function. We show that PMT-induced osteoclastogenesis is promoted by an as-yet-uncharacterized B-cell population. The toxin, however, is not acting at the level of hematopoietic stem cells, since purified CD117(+) cells from murine hematopoietic progenitor cells cultivated with PMT did not mature into osteoclasts. The early macrophages contained within this cell population (CD117(+)/CD11b(+)) did not further differentiate into osteoclasts but survived and were able to phagocytose. Within the CD117(-) population, however, we detected PMT-induced generation of a B220(+)/CD19(+) and B220(+)/IgM(+) B-cell population that was able to take up fluorescently labeled PMT. Using purified B-cell and macrophage populations, we show that these B cells are needed to efficiently generate osteoclasts from macrophages. Cells of the immune system are thought to affect osteoclast formation and function by secreting cytokines and growth factors. We show here that PMT-stimulated B cells produce elevated levels of the osteoclastogenic factors interleukin-1β (IL-1β), IL-6, tumor necrosis factor alpha, and receptor activator of nuclear factor receptor ligand (RANKL) compared to B cells generated through incubation with IL-7. These results suggest that the osteoclastic properties characteristic for PMT may result from a cross talk between bone cells and lymphoid cells and that B cells might be an important target of Pasteurella multocida.
多杀巴斯德菌是一种革兰氏阴性杆菌，能感染许多野生动物和家畜，引起呼吸道疾病。产毒多杀巴斯德菌菌株产生一种蛋白毒素（PMT），由于破骨细胞生成增强和成骨细胞功能抑制，导致猪发生萎缩性鼻炎。我们表明，PMT 诱导的破骨细胞生成是由一个尚未明确特征的 B 细胞群促进的。然而，这种毒素不是在造血干细胞水平起作用，因为从用 PMT 培养的鼠造血祖细胞中纯化的 CD117(+)细胞不会成熟为破骨细胞。该细胞群中包含的早期巨噬细胞（CD117(+)/CD11b(+））不会进一步分化为破骨细胞，但存活下来并能够吞噬。然而，在 CD117(-)群体中，我们检测到 PMT 诱导生成了一个 B220(+)/CD19(+)和 B220(+)/IgM(+)B 细胞群体，该群体能够摄取荧光标记的 PMT。使用纯化的 B 细胞和巨噬细胞群体，我们表明这些 B 细胞对于从巨噬细胞中有效生成破骨细胞是必需的。免疫系统的细胞被认为通过分泌细胞因子和生长因子来影响破骨细胞的形成和功能。我们在这里表明，与通过与 IL-7 孵育生成的 B 细胞相比，PMT 刺激的 B 细胞产生更高水平的破骨细胞生成因子白细胞介素-1β（IL-1β）、IL-6、肿瘤坏死因子-α和核因子受体配体激活剂（RANKL）。这些结果表明，PMT 特有的破骨细胞特性可能是骨细胞和淋巴细胞之间的交叉对话的结果，并且 B 细胞可能是多杀巴斯德菌的一个重要靶标。
