Department of Gastroenterology, Nan Lou Division, the PLA General Hospital, Beijing, China.
Cell Mol Immunol. 2013 Jan;10(1):78-83. doi: 10.1038/cmi.2012.32. Epub 2012 Sep 3.
T helper 2 (Th2) polarization is a major pathological feature in allergic diseases; its etiology is not fully understood. This study aims to elucidate the adjuvant effect of the microbial product-derived small peptides in the initiation of antigen-specific Th2 polarization. In this study, a clinical survey of patients with chronic rhinosinusitis (CRS) and food allergy (FA) was carried out. The Staphylococcal enterotoxin B (SEB)-derived small peptides (Ssps) were examined in the human stool extracts. The formation of Ssp/antigen adducts was tested in a protein-protein combination assay. The bone marrow-derived dendritic cells (BMDCs) were employed to test the role of Ssp/ovalbumin (OVA) adducts in the dendritic cell (DC) maturation. A mouse model was developed to test the role of Ssp/OVA adducts in the initiation of Th2 polarization in the intestine. The results showed that 54 (18.2%) patients with FA were diagnosed among 296 patients with SEB(+) CRS; only eight (2.9%) FA patients were identified among 272 patients with SEB(-) CRS. Ssps were detected in the stool protein extracts from FA patients with SEB(+) CRS, but not in those with SEB(-) CRS. Ssp/OVA adducts induced DC maturation, speeded up DC migration, activated CD4(+) T cells in the regional lymph nodes and induced skewed Th2 polarization in the local tissue. We conclude that patients with SEB(+) CRS are prone to suffering from FA. SEB can be degraded to Ssps in the gastrointestinal tract. The Ssps can bind macromolecular antigens to form adducts to promote the antigenicity of the antigens and induction of the antigen-specific Th2 polarization and inflammation in the local tissue.
辅助性 T 细胞 2(Th2)极化是过敏疾病的主要病理特征;其病因尚未完全阐明。本研究旨在阐明微生物产物衍生的小肽在启动抗原特异性 Th2 极化中的佐剂作用。本研究对慢性鼻-鼻窦炎(CRS)和食物过敏(FA)患者进行了临床调查。检测了来源于葡萄球菌肠毒素 B(SEB)的小肽(Ssp)在人类粪便提取物中的存在。在蛋白质-蛋白质结合测定中检测了 Ssp/抗原加合物的形成。采用骨髓来源的树突状细胞(BMDC)检测 Ssp/卵清蛋白(OVA)加合物在树突状细胞(DC)成熟中的作用。建立了一个小鼠模型来检测 Ssp/OVA 加合物在肠道中启动 Th2 极化的作用。结果显示,在 296 例 SEB(+)CRS 患者中诊断出 54 例(18.2%)FA 患者;在 272 例 SEB(-)CRS 患者中仅发现 8 例(2.9%)FA 患者。在 SEB(+)CRS 合并 FA 的患者粪便蛋白提取物中检测到 Ssps,但在 SEB(-)CRS 患者中未检测到。Ssp/OVA 加合物诱导 DC 成熟,加速 DC 迁移,激活局部淋巴结中的 CD4(+)T 细胞,并在局部组织中诱导偏向性 Th2 极化。我们得出结论,SEB(+)CRS 患者易患 FA。SEB 可在胃肠道中降解为 Ssps。Ssps 可以与大分子抗原结合形成加合物,从而促进抗原的抗原性,并诱导局部组织中抗原特异性 Th2 极化和炎症。