天然免疫在抗感染和抗肿瘤中至关重要，它通过诱导细胞因子表达，一方面杀灭病毒及被感染的或发生癌变的细胞，另一方面活化获得性免疫促进抗体产生和特异性淋巴细胞活化。我们在前期研究中发现锰元素在天然免疫活化中发挥重要作用，同时又是一种强烈的免疫活化剂及警报素，可以在没有任何感染的情况下激活细胞进入抗病毒状态。由于以往从未发现锰元素的免疫调节作用，目前相关的病理、生理作用研究是一个空白。而我们的这些发现又产生出许多重要而亟待解决的科学问题，主要包括1）锰元素活化炎症小体的分子机制；2）锰元素抗肿瘤功能及其分子机制；3）锰元素调节获得性免疫及作为免疫佐剂的分子机制；4）锰元素在神经系统中的病理学功能及分子机制。本申请将系统而深入地研究锰元素在多种生理病理条件下的功能，尤其是在抗感染、抗肿瘤及神经退行性疾病中的免疫调节作用，所获结果将为相关疾病的预防、治疗及锰元素作为免疫调节剂的实际应用提供理论基础。

Innate immunity plays essential roles in both anti-tumor and anti-infection processes. Through inducing specific cytokines upon stimulates, innate responses undergo killing of the invaded pathogens and tumors as the first line of host protection, as well as facilitating antibody production and maturation of lymphocytes in the adaptive immunity. Our previous work demonstrated that Mn2+, one of the essential mental cofactors inside the cell, is crucial for activation of innate responses and also works as an alarmin to provoke an elevated antiviral state without any infections. However, research on the pathological and physiological roles of manganese in the field of immunology is still poor. Thus, many important open questions are brought into concerning, including 1) molecular mechanisms of inflammasome activation triggered by Mn2+, 2) Mn2+’s contribution in anti-tumor immunity and the molecular details, 3) evaluation of manganese as an adjuvant, 4) molecular processes in pathogenesis of elevated Mn2+-associated neurodegenerative diseases. We will systematically work out how Mn2+ regulates immunological processes upon infections and cancer in both physiological and pathological levels, which provides a molecular basis for further applications of manganese as immune-regulatory drugs to treat relevant human diseases.