Innate immune recognition of molds and homology to the inner ear protein, cochlin, in patients with autoimmune inner ear disease.
Innate immune recognition of molds and homology to the inner ear protein, cochlin, in patients with autoimmune inner ear disease.
复制标题
DOI：
10.1007/s10875-013-9926-x
复制
发表时间：
2013-10
影响因子：
9.1
通讯作者：
Vambutas A
中科院分区：
文献类型：
--
作者：
Pathak S;Hatam LJ;Bonagura V;Vambutas A
自身免疫性内耳疾病（AIED）的特征是双侧波动性感音神经性听力损失，伴有由未知刺激引发的听力下降。在这里，我们研究了这些AIED患者的环境暴露于霉菌是否足以产生促炎反应，这可能部分解释疾病急性加重期。我们假设，霉菌可能会刺激这些患者的异常免疫反应，因为几种曲霉菌和青霉菌与内耳蛋白cochlin的LCCL结构域具有同源性。我们发现，与对照组相比，AIED患者血浆中1：256稀释度的抗霉菌IgG（p=0.032）和1：256稀释度的抗cochlin IgG（p=0.0094和1：512稀释度的p=0.024）水平较高。AIED患者的外周血单个核细胞（PBMC）暴露于霉菌导致IL-1β mRNA表达上调，在霉菌敏感的AIED患者中IL-1β和IL-6分泌增加，并产生表达IL-17的细胞，表明霉菌在这些患者的一个子集中充当PAMP。当用霉菌提取物处理的AIED患者单核细胞的条件上清液刺激时，幼稚B细胞分泌IgM。总之，目前的研究表明，真菌暴露可以触发自身免疫性疾病易感患者的一个子集。
Autoimmune Inner Ear Disease (AIED) is characterized by bilateral, fluctuating sensorineural hearing loss with periods of hearing decline triggered by unknown stimuli. Here we examined whether an environmental exposure to mold in these AIED patients is sufficient to generate a pro-inflammatory response that may, in part, explain periods of acute exacerbation of disease. We hypothesized that molds may stimulate an aberrant immune response in these patients as both several Aspergillus species and penecillium share homology with the LCCL domain of the inner ear protein, cochlin. We showed the presence of higher levels of anti-mold IgG in plasma of AIED patients at dilution of 1:256 (p=0.032) and anti-cochlin IgG 1:256 (p=0.0094 and at 1:512 p=0.024) as compared with controls. Exposure of peripheral blood mononuclear cells (PBMC) of AIED patients to mold resulted in an up-regulation of IL-1β mRNA expression, enhanced IL-1β and IL-6 secretion, and generation of IL-17 expressing cells in mold-sensitive AIED patients, suggesting mold acts as a PAMP in a subset of these patients. Naïve B cells secreted IgM when stimulated with conditioned supernatant from AIED patients’ monocytes treated with mold extract. In conclusion, the present studies indicate that fungal exposure can trigger autoimmunity in a subset of susceptible AIED patients.
登录
查看更多内容
影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
3.7
作者：
Gazquez I;Soto-Varela A;Aran I;Santos S;Batuecas A;Trinidad G;Perez-Garrigues H;Gonzalez-Oller C;Acosta L;Lopez-Escamez JA
通讯作者：
Lopez-Escamez JA
DOI：
10.1084/jem.191.2.313
发表时间：
2000-01-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Horai R;Saijo S;Tanioka H;Nakae S;Sudo K;Okahara A;Ikuse T;Asano M;Iwakura Y
通讯作者：
Iwakura Y
影响因子：
64.8
作者：
HIRANO, T;YASUKAWA, K;KISHIMOTO, T
通讯作者：
KISHIMOTO, T
影响因子：
4.4
作者：
Bozza, Silvia;Zelante, Teresa;Romani, Luigina
通讯作者：
Romani, Luigina