美国杜克大学医学院E. Ashley Moseman团队近期取得重要工作进展，他们研究发现粘膜浆细胞能够保护上呼吸道和大脑免受感染。这一研究成果于2022年9月21日在线发表于《免疫学》杂志上。

在小鼠中使用多种病毒感染模型，研究人员发现血源性抗体无法保护嗅觉上皮。尽管血清抗体滴度很高，但病原体感染了鼻甲，并且嗜神经微生物侵入了大脑。使用被动抗体转移和联体共生，研究人员确定了一个限制性的血液内皮屏障，它排除了嗅粘膜中的循环抗体。浆细胞耗竭表明浆细胞必须存在于嗅觉组织内才能实现杀菌免疫。抗体阻断和基因缺陷模型表明，这种局部免疫需要CD4⁺ T细胞和CXCR3。许多疫苗佐剂未能产生嗅浆细胞，但黏膜免疫对嗅觉表面建立了体液保护。研究人员对血液嗅觉屏障的鉴定和对组织来源抗体的需求对疫苗学、呼吸道和中枢神经系统病原体传播以及B细胞命运决定具有重要意义。

据介绍，虽然血液抗体介导大多数器官的保护性免疫，但它们是否保护上呼吸道的鼻表面尚不清楚。

附：英文原文

Title: Mucosal plasma cells are required to protect the upper airway and brain from infection

Author: Sebastian A. Wellford, Annie Park Moseman, Kianna Dao, Katherine E. Wright, Allison Chen, Jona E. Plevin, Tzu-Chieh Liao, Naren Mehta, E. Ashley Moseman

Issue&Volume: 2022-09-21

Abstract: While blood antibodies mediate protective immunity in most organs, whether they protectnasal surfaces in the upper airway is unclear. Using multiple viral infection modelsin mice, we found that blood-borne antibodies could not defend the olfactory epithelium.Despite high serum antibody titers, pathogens infected nasal turbinates, and neurotropicmicrobes invaded the brain. Using passive antibody transfers and parabiosis, we identifieda restrictive blood-endothelial barrier that excluded circulating antibodies fromthe olfactory mucosa. Plasma cell depletions demonstrated that plasma cells must residewithin olfactory tissue to achieve sterilizing immunity. Antibody blockade and geneticallydeficient models revealed that this local immunity required CD4+ T cells and CXCR3. Many vaccine adjuvants failed to generate olfactory plasma cells,but mucosal immunizations established humoral protection of the olfactory surface.Our identification of a blood-olfactory barrier and the requirement for tissue-derivedantibody has implications for vaccinology, respiratory and CNS pathogen transmission,and B cell fate decisions.

DOI: 10.1016/j.immuni.2022.08.017

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00411-3