致死性中线肉芽肿的真菌感染病因及致病机制研究

Lethal midline granuloma (LMG) is a middle face destruction with unknown aetiology. The disease has been considered as NK/T cell lymphoma for natural killer cells or T cells aggregation have been seen in tissue. However, patients treated with anti-cancer therapy often died after a short remission. During the previous work, we surprisingly found that Mucor irregularis associated rhino-orbital-cerebral mycosis could manifest as the same clinical-pathological characteristic as that in LMG that might be cured with mere antifungal therapy. Further investigation showed that it is difficult to recognize the fungi in tissues of ROCM because of their variety in shape. The NK/T cells might also appear in the pathologic tissue of ROCM. We thought, for the first time, that fungal infection might be one of the aetilogical agents, and the NK/T cells in tissue would be immune responding cells rather than malignant cells. In the project, we aim to study the morphology of ROCM fungi in tissues and characterize the aggregated inflammatory cells in ROCM with animal experiments. We hope to figure out if the angiocentric and angioinvasive characteristics in LMG could be induced by fungal infection. We will also study different growth forms of fungi in the tissue of ROCM and that in the experimental animals. Furthermore, we will reveal the interaction of NK/T cells and ROCM fungi, the mechanisms of NK/T cells infiltration in tissue that might be atypical. In the end, we hope to prove that LMG and ROCM might share the same aetiological agents, or at least, parts of them.

致死性中线肉芽肿（LMG）为面部中线部位的损毁性破坏，该病病因一直不明，后因在组织中发现NK/T细胞而被认为是NK/T细胞淋巴瘤，但是病人经抗肿瘤治疗后多经短暂缓解后死亡。我们前期研究发现毛霉等真菌感染而致的鼻眶脑真菌病（ROCM）可出现与LMG相似的临床病理表现，单纯抗真菌治疗后可获痊愈。进一步研究发现ROCM致病菌在组织中变异较大，难以辨认；真菌感染后可出现NK/T细胞浸润。有鉴于此，我们在国际上首次提出真菌感染可能为LMG的病因之一，病理组织中NK/T细胞应为免疫效应细胞。本研究拟通过动物实验验证ROCM致病菌在组织中的表现形式及其所诱发的炎性细胞的性质；感染后是否可以诱导出血管中心性病变等LMG特点；通过细胞学方法探索ROCM致病菌与NK/T细胞等LMG中重要炎症细胞的交互作用，NK/T细胞受真菌激发后增殖与非典型改变的机制，为揭示ROCM与LMG相关性，提供系统、科学的实验依据。

致死性中线肉芽肿（LMG）为面部中线部位的损毁性破坏，该病病因一直不明，后因在组织中发现NK/T细胞而被认为是NK/T细胞淋巴瘤，但是，病人经抗肿瘤治疗后多经短暂缓解后死亡。我们前期研究发现毛霉等真菌感染而致的鼻眶脑真菌病（ROCM）可出现与LMG相似的临床病理表现，单纯抗真菌治疗后可获痊愈。进一步研究发现，ROCM致病菌在组织中变异较大，难以辨认；真菌感染后可出现NK/T细胞浸润。有鉴于此，我们在国际上首次提出真菌感染可能为LMG的病因之一，病理组织中NK/T细胞应为免疫效应细胞。本研究拟通过动物实验验证ROCM致病菌在组织中的表现形式及其所诱发的炎性细胞的性质；感染后是否可以诱导出血管中心性病变等LMG特点；通过细胞学方法探索ROCM致病菌与NK/T细胞等LMG中重要炎症细胞的交互作用，NK/T细胞受真菌激发后增殖与非典型改变的机制，为揭示ROCM与LMG相关性，提供系统、科学的实验依据。

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