Wu Xia-Nan, Dong Ke, Liu Yan, Yang Lan, Zhang Jing, Yang Ming, Gao Zhao-Wei
Department of Clinical Laboratory, Tangdu Hospital, Airforce Medical University, Xi'an, Shaanxi, People's Republic of China.
J Inflamm Res. 2025 Mar 6;18:3283-3294. doi: 10.2147/JIR.S501546. eCollection 2025.
The incidence of candidemia, mediated by systemic () infection, was increasing. It is an urgent need to understand the underlying disease mechanisms to identify new therapeutic targets. This study aimed to investigate the roles of adenosine-adenosine receptor signal in systemic infection.
The candidemia mice models (named CA mice) were established by tail intravenous injection of . CA Mice were treated with NECA (a metabolically stable adenosine analogue) or agonists targeting different adenosine receptors (A1R, A2AR, A2BR and A3R). The survival rate, renal fungal load and tissue damage were investigated. Bone marrow-derived macrophages (BMDM) were isolated and cultured to investigate the effects of NECA and adenosine receptor agonist on phagocytosis, killing function and polarization of macrophages.
In CA mice, we observed that NECA and A2AR agonist treatment significantly alleviated the sepsis score and increased the survival rate. Moreover, the renal injury and fungal load were reduced by NECA and A2AR agonist treatment. However, the other adenosine receptors (ie, A1R, A2BR and A3R) activation have no effect on survival and tissue damage of CA mice. A2AR activation could reduce macrophage infiltration in kidney and the production of inflammatory cytokine IL-6 in CA mice. Moreover, adenosine-A2AR signaling activation could enhance antifungal capacity of macrophages and promoted macrophage polarization toward the M2 subtype.
Activation of adenosine-A2AR axis promoted macrophage M2 polarization, enhanced host defense against systemic infection, and alleviated candidiasis. A2AR activation could be considered as a potential therapeutic strategy in candidemia.
由全身性（）感染介导的念珠菌血症发病率正在上升。迫切需要了解潜在的疾病机制以确定新的治疗靶点。本研究旨在探讨腺苷 - 腺苷受体信号在全身性感染中的作用。
通过尾静脉注射建立念珠菌血症小鼠模型（命名为CA小鼠）。用NECA（一种代谢稳定的腺苷类似物）或靶向不同腺苷受体（A1R、A2AR、A2BR和A3R）的激动剂处理CA小鼠。研究存活率、肾脏真菌负荷和组织损伤情况。分离并培养骨髓来源的巨噬细胞（BMDM），以研究NECA和腺苷受体激动剂对巨噬细胞吞噬作用、杀伤功能和极化的影响。
在CA小鼠中，我们观察到NECA和A2AR激动剂治疗显著减轻了脓毒症评分并提高了存活率。此外，NECA和A2AR激动剂治疗降低了肾脏损伤和真菌负荷。然而，其他腺苷受体（即A1R、A2BR和A3R）的激活对CA小鼠的存活和组织损伤没有影响。A2AR激活可减少CA小鼠肾脏中的巨噬细胞浸润以及炎性细胞因子IL - 6的产生。此外，腺苷 - A2AR信号激活可增强巨噬细胞的抗真菌能力，并促进巨噬细胞向M2亚型极化。
腺苷 - A2AR轴的激活促进巨噬细胞M2极化，增强宿主对全身性感染的防御，并减轻念珠菌病。A2AR激活可被视为念珠菌血症的一种潜在治疗策略。
