RIKEN Center for Integrative Medical Sciences (IMS), Kanagawa, Japan.
Graduate School of Medical Life Science, Yokohama City University, Kanagawa, Japan.
Int Immunol. 2017 Dec 18;29(10):471-478. doi: 10.1093/intimm/dxx064.
Nasopharynx-associated lymphoid tissue (NALT) is one of the major constituents of the mucosa-associated lymphoid tissue (MALT), and has the ability to induce antigen-specific immune responses. However, the molecular mechanisms responsible for antigen uptake from the nasal cavity into the NALT remain largely unknown. Immunohistochemical analysis showed that CCL9 and CCL20 were co-localized with glycoprotein 2 (GP2) in the epithelium covering NALT, suggesting the existence of M cells in NALT. In analogy with the reduced number of Peyer's patch M cells in CCR6-deficient mice, the number of NALT M cells was drastically decreased in CCR6-deficient mice compared with the wild-type mice. Translocation of nasally administered Salmonella enterica serovar Typhimurium into NALT via NALT M cells was impaired in CCR6-deficient mice, whereas S. Typhimurium demonstrated consistent co-localization with NALT M cells in wild-type mice. When wild-type mice were nasally administered with an attenuated vaccine strain of S. Typhimurium, the mice were protected from a subsequent challenge with wild-type S. Typhimurium. Antigen-specific fecal and nasal IgA was detected after nasal immunization with the attenuated vaccine strain of S. Typhimurium only in wild-type mice but not in CCR6-deficient mice. Taken together, these observations demonstrate that NALT M cells are important as a first line of defense against infection by enabling activation of the common mucosal immune system (CMIS).
鼻咽相关淋巴组织 (NALT) 是黏膜相关淋巴组织 (MALT) 的主要组成部分之一,具有诱导抗原特异性免疫反应的能力。然而,将鼻腔中的抗原摄取到 NALT 中的分子机制在很大程度上仍然未知。免疫组织化学分析显示,CCL9 和 CCL20 与 NALT 上皮覆盖的糖蛋白 2 (GP2) 共定位,提示 NALT 中存在 M 细胞。与 CCR6 缺陷型小鼠派尔集合淋巴结 M 细胞数量减少类似,NALT M 细胞数量在 CCR6 缺陷型小鼠中明显减少与野生型小鼠相比。通过 NALT M 细胞将鼻腔给予的沙门氏菌血清型 Typhimurium 易位到 NALT 的能力在 CCR6 缺陷型小鼠中受损,而沙门氏菌血清 Typhimurium 在野生型小鼠中与 NALT M 细胞一致共定位。当野生型小鼠鼻腔给予沙门氏菌血清型 Typhimurium 的减毒疫苗株时,这些小鼠在随后用野生型 Typhimurium 沙门氏菌攻击时受到保护。仅在野生型小鼠中,而不是在 CCR6 缺陷型小鼠中,通过鼻腔免疫减毒疫苗株沙门氏菌血清型 Typhimurium 后,可检测到抗原特异性粪便和鼻内 IgA。总之,这些观察结果表明,NALT M 细胞作为第一道防线对感染很重要,因为它能够激活共同黏膜免疫系统 (CMIS)。