Targeted delivery of antigen to hamster nasal lymphoid tissue with M-cell-directed lectins
Targeted delivery of antigen to hamster nasal lymphoid tissue with M-cell-directed lectins
复制标题
DOI：
10.1128/iai.65.10.4288-4298.1997
复制
发表时间：
1997-10-01
影响因子：
3.1
通讯作者：
Monath, TP
中科院分区：
文献类型：
--
作者：
Giannasca, PJ;Boden, JA;Monath, TP
啮齿类动物的鼻腔内衬有上皮，上皮组织成负责特定生理功能的不同区域，位于鼻腔底部的鼻淋巴组织（NALT）聚集体被认为是诱导对空气传播抗原的粘膜免疫应答的位点，覆盖NALT的上皮含有专门用于免疫原转胞吞的M细胞，如在其他粘膜组织中所证实的，我们假设NALT M细胞的特征在于不同的糖缀合物受体，其影响抗原摄取和对转胞吞抗原的免疫应答。为了鉴定可以将NALT M细胞与呼吸上皮（RE）的其他细胞区分开的糖缀合物，我们用一组凝集素对仓鼠鼻腔的切片进行了凝集素组织化学，在该区域的上皮细胞上发现了许多种类的糖缀合物。虽然大多数凝集素结合到RE和M细胞上的位点，但发现能够识别顺式连接的半乳糖的探针几乎仅标记滤泡相关上皮（FAE）。根据形态学标准，FAE含有>90%的M细胞。为了确定M细胞上的顶端糖缀合物是否可从鼻腔接近，将M细胞选择性凝集素和对照凝集素平行鼻内给予仓鼠。发现M细胞选择性凝集素特异性地靶向FAE，而对照凝集素没有。在体内结合到M细胞的凝集素被有效地内吞，这与hi细胞在抗原转运中的作用一致。用凝集素测试抗原缀合物鼻内免疫而没有佐剂刺激特异性血清免疫球蛋白G的诱导，而单独的抗原或与凝集素混合的抗原没有。NALT M细胞在体内通过凝集素的选择性识别提供了M细胞上的微生物粘附素-宿主细胞受体相互作用和鼻内给药后免疫原靶向递送至NALT的模型。
The nasal cavity of a rodent is lined by an epithelium organized into distinct regional domains responsible for specific physiological functions, Aggregates of nasal lymphoid tissue (NALT) located at the base of the nasal cavity are believed to be sites of induction of mucosal immune responses to airborne antigens, The epithelium overlying NALT contains M cells which are specialized for the transcytosis of immunogens, as demonstrated in other mucosal tissues, We hypothesized that NALT M cells are characterized by distinct glycoconjugate receptors which influence antigen uptake and immune responses to transcytosed antigens, To identify glycoconjugates that may distinguish NALT M cells from other cells of the respiratory epithelium (RE), we performed lectin histochemistry on sections of the hamster nasal cavity with a panel of lectins, Many classes of glycoconjugates were found on epithelial cells in this region. While most lectins bound to sites on both the RE and M cells, probes capable of recognizing cw-linked galactose were found to label the follicle-associated epithelium (FAE) almost exclusively, By morphological criteria, the FAE contains >90% M cells, To determine if apical glycoconjugates on M cells were accessible from the nasal cavity, an M-cell-selective lectin and a control lectin in parallel were administered intranasally to hamsters. The M-cell-selective lectin was found to specifically target the FAE, while the control lectin did not, Lectin bound to M cells in vivo was efficiently endocytosed, consistent with the role of hi cells in antigen transport, Intranasal immunization with lectin-test antigen conjugates without adjuvant stimulated induction of specific serum immunoglobulin G, whereas antigen alone or admixed with lectin did not. The selective recognition of NALT M cells by a lectin in vivo provides a model for microbial adhesin-host cell receptor interactions on M cells and the targeted delivery of immunogens to NALT following intranasal administration.