Gao Peisong
Department of Medicine, Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Clin Dev Immunol. 2012;2012:563760. doi: 10.1155/2012/563760. Epub 2012 Jan 9.
Asthma is a major public health concern. Cockroach allergen exposure and cockroach allergic sensitization could contribute to the higher prevalence of asthma. However, the underlying immune mechanism and the genetic etiology remain unclear. Recent advances have demonstrated that several receptors (PAR-2, TLRs, CLRs) and their pathways mediate antigen uptake from the environment and induce allergies by signaling T cells to activate an inappropriate immune response. Cockroach-derived protease can disturb airway epithelial integrity via PAR-2 and leads to an increased penetration of cockroach allergen, resulting in activation of innate immune cells (e.g., DCs) via binding to either TLRs or CLRs. The activated DCs can direct cells of the adaptive immune system to facilitate promotion of Th2 cell response and subsequently increase risk of sensitization. Mannose receptor (MR), as a CLR, has been shown to mediate Bla g2 (purified cockroach allergen) uptake by DCs and to determine allergen-induced T cell polarization. Additionally, genetic factors may play an important role in conferring the susceptibility to cockroach sensitization. Several genes have been associated with cockroach sensitization and related phenotypes (HLA-D, TSLP, IL-12A, MBL2). In this review, we have focused on studies on the cockroach allergen induced immunologic responses and genetic basis for cockroach sensitization.
哮喘是一个主要的公共卫生问题。接触蟑螂过敏原和对蟑螂过敏致敏可能导致哮喘的较高患病率。然而,潜在的免疫机制和遗传病因仍不清楚。最近的进展表明,几种受体(PAR-2、TLRs、CLRs)及其信号通路介导从环境中摄取抗原,并通过向T细胞发出信号以激活不适当的免疫反应来诱发过敏。蟑螂来源的蛋白酶可通过PAR-2破坏气道上皮完整性,并导致蟑螂过敏原的渗透增加,从而通过与TLRs或CLRs结合激活天然免疫细胞(如树突状细胞)。活化的树突状细胞可引导适应性免疫系统的细胞促进Th2细胞反应,进而增加致敏风险。甘露糖受体(MR)作为一种CLR,已被证明可介导树突状细胞摄取Bla g2(纯化的蟑螂过敏原)并决定过敏原诱导的T细胞极化。此外,遗传因素可能在赋予蟑螂致敏易感性方面起重要作用。几个基因已与蟑螂致敏及相关表型(HLA-D、TSLP、IL-12A、MBL2)相关联。在本综述中,我们重点关注了蟑螂过敏原诱导的免疫反应以及蟑螂致敏的遗传基础的研究。