The soluble pattern recognition receptor PTX3 links humoral innate and adaptive immune responses by helping marginal zone B cells.
The soluble pattern recognition receptor PTX3 links humoral innate and adaptive immune responses by helping marginal zone B cells.
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DOI：
10.1084/jem.20150282
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发表时间：
2016-09-19
期刊：
影响因子：
--
通讯作者：
Cerutti A
中科院分区：
文献类型：
--
作者：
Chorny A;Casas-Recasens S;Sintes J;Shan M;Polentarutti N;García-Escudero R;Walland AC;Yeiser JR;Cassis L;Carrillo J;Puga I;Cunha C;Bastos H;Rodrigues F;Lacerda JF;Morais A;Dieguez-Gonzalez R;Heeger PS;Salvatori G;Carvalho A;Garcia-Sastre A;Blander JM;Mantovani A;Garlanda C;Cerutti A
Cerutti 及其合作者表明，先天性和适应性免疫系统的体液臂通过 pentraxin 3 在功能上相互连接，pentraxin 3 是一种可溶性模式识别受体，可将先天性免疫识别与抗体诱导功能结合起来。 Pentraxin 3 (PTX3) 是体液先天免疫系统的一种液相模式识别受体，具有祖先抗体样特性，但抗体诱导功能未知。在这项研究中，我们发现 PTX3 与脾边缘区 (MZ) B 细胞结合，这是一种产生抗体的淋巴细胞的先天性子集，战略性地位于循环系统和适应性免疫系统之间的界面。 PTX3 由脾 MZ 周围的一组中性粒细胞释放，并表达与循环中性粒细胞不同的免疫激活相关基因特征。 PTX3 的结合促进了微生物荚膜多糖的 IgM 和类别转换 IgG 抗体的稳态产生，在 PTX3 缺陷的小鼠和人类中，这种抗体的产生减少。此外，在感染血源性荚膜细菌或用细菌碳水化合物免疫后，PTX3 增加了 IgM 和 IgG 的产生。这种免疫原性效应源于 MZ B 细胞通过中性粒细胞调节途径的激活，该途径通过 T 细胞非依赖性和 T 细胞依赖性信号的组合引发类别转换和浆母细胞扩增。因此，PTX3 可以通过充当 MZ B 细胞的内源佐剂来桥接先天性和适应性免疫系统的体液臂。可以利用这一特性来开发针对封装病原体的更有效的疫苗。
Cerutti and collaborators show that the humoral arms of the innate and adaptive immune systems are functionally interconnected by pentraxin 3, a soluble pattern recognition receptor that couples innate immune recognition with antibody-inducing function. Pentraxin 3 (PTX3) is a fluid-phase pattern recognition receptor of the humoral innate immune system with ancestral antibody-like properties but unknown antibody-inducing function. In this study, we found binding of PTX3 to splenic marginal zone (MZ) B cells, an innate-like subset of antibody-producing lymphocytes strategically positioned at the interface between the circulation and the adaptive immune system. PTX3 was released by a subset of neutrophils that surrounded the splenic MZ and expressed an immune activation–related gene signature distinct from that of circulating neutrophils. Binding of PTX3 promoted homeostatic production of IgM and class-switched IgG antibodies to microbial capsular polysaccharides, which decreased in PTX3-deficient mice and humans. In addition, PTX3 increased IgM and IgG production after infection with blood-borne encapsulated bacteria or immunization with bacterial carbohydrates. This immunogenic effect stemmed from the activation of MZ B cells through a neutrophil-regulated pathway that elicited class switching and plasmablast expansion via a combination of T cell–independent and T cell–dependent signals. Thus, PTX3 may bridge the humoral arms of the innate and adaptive immune systems by serving as an endogenous adjuvant for MZ B cells. This property could be harnessed to develop more effective vaccines against encapsulated pathogens.
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影响因子：
64.5
作者：
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通讯作者：
Park, CG
影响因子：
64.5
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作者：
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