Inflammatory Monocytes Are Critical for Induction of a Polysaccharide-Specific Antibody Response to an Intact Bacterium
Inflammatory Monocytes Are Critical for Induction of a Polysaccharide-Specific Antibody Response to an Intact Bacterium
复制标题
DOI：
10.4049/jimmunol.1202455
复制
发表时间：
2013-02-01
影响因子：
4.4
通讯作者：
Snapper, Clifford M.
中科院分区：
文献类型：
--
作者：
Chen, Quanyi;Snapper, Clifford M.
尽管炎症单核细胞(IM)(CD11b(+)Ly6C hi细胞)已被证明在细胞介导的宿主抵抗细胞内细菌、原生动物和真菌的保护中发挥重要作用，但它们对细胞外细菌的体液免疫反应的潜在影响尚不清楚。CD11b-白喉毒素(DT)受体骨髓嵌合小鼠脾边缘的IM在DT治疗后选择性地被耗尽，包括不减少CD11b(+)的腹膜B细胞。去除IM导致对完整的热致死肺炎链球菌的多糖(PS)特异性、T细胞非依赖性的IgM和T细胞依赖性的免疫球蛋白反应显著降低，而对相关的肺炎链球菌蛋白特异性的免疫球蛋白应答或对可溶性肺炎球菌结合疫苗的PS和蛋白质特异性的免疫球蛋白应答没有影响。免疫球蛋白主要在肺炎链球菌免疫反应启动后的48小时内产生PS特异性的IgM和Ig G。将高纯度的IM从野生型小鼠过继转移到DT治疗的CD11b-DT受体小鼠中，完全恢复了对肺炎链球菌的PS特异性免疫球蛋白G反应。IM在表型和功能上不同于循环中的CD11b(+)CD11c(Low)Ly6G/C细胞(未成熟的血树突状细胞)，因为它们是CD11c(-)和Ly6C(Hi)，并且在反应的早期阶段不内化注射的肺炎链球菌。据我们所知，这些数据是第一次确定IM在诱导对完整的胞外细菌的免疫球蛋白应答中的关键作用。免疫学杂志，2013,190：1048-1055。
Although inflammatory monocytes (IM) (CD11b(+)Ly6C hi cells) have been shown to play important roles in cell-mediated host protection against intracellular bacteria, protozoans, and fungi, their potential impact on humoral immune responses to extracellular bacteria are unknown. IM, localized largely to the splenic marginal zone of naive CD11b-diphtheria toxin (DT) receptor bone marrow-chimeric mice were selectively depleted following treatment with DT, including no reduction of CD11b(+) peritoneal B cells. Depletion of IM resulted in a marked reduction in the polysaccharide (PS)-specific, T cell-independent IgM, and T cell-dependent IgG responses to intact, heat-killed Streptococcus pneumoniae with no effect on the associated S. pneumoniae protein-specific IgG response or on the PS-and protein-specific IgG responses to a soluble pneumococcal conjugate vaccine. IM acted largely within the first 48 h following the initiation of the immune response to S. pneumoniae to induce the subsequent production of PS-specific IgM and IgG. Adoptive transfer of highly purified IM from wild-type mice into DT-treated CD11b-DT receptor mice completely restored the defective PS-specific IgG response to S. pneumoniae. IM were phenotypically and functionally distinct from circulating CD11b(+)CD11c(low)Ly6G/C cells (immature blood dendritic cells), previously described to play a role in Ig responses to S. pneumoniae, in that they were CD11c(-) as well as Ly6C(hi) and did not internalize injected S. pneumoniae during the early phase of the response. These data are the first, to our knowledge, to establish a critical role for IM in the induction of an Ig response to an intact extracellular bacterium. The Journal of Immunology, 2013, 190: 1048-1055.