Complement is a key component of the immune system with roles in inflammation and host-defence. Here we reveal novel functions of complement pathways impacting on emotional reactivity of potential relevance to the emerging links between complement and risk for psychiatric disorder. We used mouse models to assess the effects of manipulating components of the complement system on emotionality. Mice lacking the complement C3a Receptor (C3aR^−/−) demonstrated a selective increase in unconditioned (innate) anxiety whilst mice deficient in the central complement component C3 (C3^−/−) showed a selective increase in conditioned (learned) fear. The dissociable behavioural phenotypes were linked to different signalling mechanisms. Effects on innate anxiety were independent of C3a, the canonical ligand for C3aR, consistent with the existence of an alternative ligand mediating innate anxiety, whereas effects on learned fear were due to loss of iC3b/CR3 signalling. Our findings show that specific elements of the complement system and associated signalling pathways contribute differentially to heightened states of anxiety and fear commonly seen in psychopathology.

补体是免疫系统的关键组成部分，在炎症和宿主防御中发挥作用。在这里，我们揭示了补体途径影响情绪反应的新功能，这与补体与精神疾病风险之间的新兴联系可能相关。我们使用小鼠模型来评估操纵补体系统成分对情绪的影响。缺乏补体 C3a 受体 ( C3aR ^-/- ) 的小鼠表现出选择性增加非条件性（先天）焦虑，而缺乏中央补体成分 C3 ( C3 ^-/-的小鼠) 表现出条件性（习得性）恐惧的选择性增加。可分离的行为表型与不同的信号机制有关。对先天性焦虑的影响与 C3a（C3aR 的典型配体）无关，这与介导先天性焦虑的替代配体的存在一致，而对学习恐惧的影响是由于 iC3b/CR3 信号传导的丧失。我们的研究结果表明，补体系统的特定元素和相关的信号通路对精神病理学中常见的焦虑和恐惧状态的升高有不同的贡献。