Trehalose Dimycolate Elicits Eosinophilic Skin Hypersensitivity in Mycobacteria-Infected Guinea Pigs
Trehalose Dimycolate Elicits Eosinophilic Skin Hypersensitivity in Mycobacteria-Infected Guinea Pigs
复制标题
DOI：
10.4049/jimmunol.181.12.8528
复制
发表时间：
2008-12-15
影响因子：
4.4
通讯作者：
Sugita, Masahiko
中科院分区：
文献类型：
--
作者：
Otsuka, Atsushi;Matsunaga, Isamu;Sugita, Masahiko
迟发型超敏反应代表由分枝杆菌感染诱导的高水平蛋白Ag特异性适应性免疫，并且可以在Ag激发的皮肤中监测。除了蛋白质Ags，最近的证据表明，针对糖脂Ags的大量免疫也引起了对分枝杆菌感染的反应，但皮肤对这类Ags的超敏反应尚未得到充分评估。为了直接解决这一问题，在感染鸟分枝杆菌复合群（MAC）的豚鼠中评价了糖脂特异性皮肤反应。在皮内给予MAC衍生的糖脂混合物后，在MAC感染但非模拟感染的豚鼠中观察到显著的皮肤硬结。令人惊讶的是，这种糖脂特异性皮肤反应涉及IL-5 mRNA原位表达上调和显著的嗜酸性粒细胞局部浸润。用单个糖脂组分进行的挑战实验检测到海藻糖二霉菌酸盐（TDM）引起皮肤反应的出色能力，但不是结构相关的糖脂葡萄糖单霉菌酸盐。T淋巴细胞来自MAC感染的脾脏，但不是未感染的，豚鼠特异性地响应TDM在体外上调IL-5的转录，这种反应并没有被阻断的抗体反应，已知的豚鼠组1 CD 1蛋白。最后，嗜酸性皮肤超敏反应TDM也引起接种卡介苗，这与经典的迟发型超敏反应的纯化蛋白衍生物形成鲜明对比的豚鼠。因此，TDM引起的嗜酸性粒细胞反应定义了分枝杆菌感染中的一种新形式的超敏反应，这可能是感染部位经常观察到的嗜酸性粒细胞局部浸润的原因。免疫学杂志，2008，181：8528-8533.
Delayed-type hypersensitivity represents high levels of protein Ag-specific adaptive immunity induced by mycobacterial infection, and can be monitored in the Ag-challenged skin. Besides protein Ags, recent evidence has suggested that a substantial immunity directed against glycolipid Ags is also elicited in response to mycobacterial infection, but skin hypersensitivity to this class of Ags has not been fully assessed. To address this issue directly, glycolipid-specific skin reactions were evaluated in guinea pigs infected with Mycobacterium avium complex (MAC). Significant skin induration was observed in MAC-infected, but not mock-infected, guinea pigs, following intradermal administration of a mixture of MAC-derived glycolipids. Surprisingly, this glycolipid-specific skin response involved up-regulated expression of IL-5 mRNA in situ and marked local infiltration of eosinophils. Challenge experiments with individual glycolipid components detected an outstanding capability for trehalose dimycolate (TDM), but not a structurally related glycolipid, glucose monomycolate, to elicit the skin response. T lymphocytes derived from the spleen of MAC-infected, but not uninfected, guinea pigs specifically responded to TDM in vitro by up-regulating IL-5 transcription, and this response was not blocked by Abs that reacted to the known guinea pig group 1 CD1 proteins. Finally, the eosinophilic skin hypersensitivity to TDM was also elicited in guinea pigs vaccinated with bacillus Calmette-Guerin, which contrasted sharply with the classical delayed-type hypersensitivity response to the purified protein derivative. Therefore, the TDM-elicited eosinophilic response defines a new form of hypersensitivity in mycobacterial infection, which may account for local infiltration of eosinophils often observed at the site of infection. The Journal of Immunology, 2008, 181: 8528-8533.