Trehalose Dimycolate Elicits Eosinophilic Skin Hypersensitivity in Mycobacteria-Infected Guinea Pigs1
Trehalose Dimycolate Elicits Eosinophilic Skin Hypersensitivity in Mycobacteria-Infected Guinea Pigs1
复制标题
海藻糖二霉菌酸酯引起分枝杆菌感染的豚鼠嗜酸性皮肤过敏1
作者：
A. Otsuka;I. Matsunaga;T. Komori;K. Tomita;Y. Toda;T. Manabe;Y. Miyachi;M. Sugita
迟发性超敏反应代表着由分枝杆菌感染诱导的高水平的蛋白Ag特异性适应性免疫，可以在Ag挑战的皮肤中监测到。除了蛋白质AGS，最近的证据表明，针对糖脂AGS的实质性免疫也是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。为了直接解决这个问题，我们评估了感染禽型分枝杆菌复合体(MAC)的豚鼠的糖脂特异性皮肤反应。皮内注射MAC衍生的糖脂混合物后，在感染MAC的豚鼠中观察到显著的皮肤硬化，但在模拟感染的豚鼠中没有观察到。令人惊讶的是，这种糖脂特异性的皮肤反应涉及IL-5mRNA的原位上调表达和明显的局部嗜酸性粒细胞的渗透。用单个糖脂成分进行的挑战实验发现，海藻糖二乙醇酸盐(TDM)具有出色的能力，但不是一种结构相关的糖脂，即葡萄糖单甲酸酯，可以引发皮肤反应。感染但不感染MAC的豚鼠脾中的T淋巴细胞在体外通过上调IL-5转录对TDM产生特异性反应，这种反应不能被与已知的豚鼠第1组CD1蛋白反应的抗体所阻断。最后，在接种卡介苗的豚鼠中也出现了嗜酸性皮肤对TDM的超敏反应，这与传统的对纯化蛋白衍生物的迟发性超敏反应形成了鲜明的对比。因此，TDM诱导的嗜酸性粒细胞反应定义了分枝杆菌感染的一种新的超敏反应，这可能是感染部位经常观察到的嗜酸性粒细胞局部渗透的原因。
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.
影响因子：
56.9
作者：
Moody, DB;Reinhold, BB;Porcelli, SA
通讯作者：
Porcelli, SA
豚鼠 CD1 多基因家族的保护。
DOI：
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发表时间：
1999
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Dascher,CC;Hiromatsu,K;Naylor,JW;Brauer,PP;Brown,KA;Storey,JR;Behar,SM;Kawasaki,ES;Porcelli,SA;Brenner,MB;LeClair,KP
通讯作者：
LeClair,KP