Goli Sri Harshini, Lim Joo-Yeon, Basaran-Akgul Nese, Templeton Steven P
Department of Microbiology and Immunology, Indiana University School of Medicine-Terre Haute, Terre Haute, Indiana, United States of America.
Department of Biology, Indiana State University, Terre Haute, Indiana, United States of America.
PLoS Pathog. 2025 Mar 17;21(3):e1012363. doi: 10.1371/journal.ppat.1012363. eCollection 2025 Mar.
Although innate immunity is critical for antifungal host defense against the human opportunistic fungal pathogen Aspergillus fumigatus, potentially damaging inflammation must be controlled. Adiponectin (APN) is an adipokine produced mainly in adipose tissue that exerts anti-inflammatory effects in adipose-distal tissues such as the lung. We observed increased mortality and increased fungal burden and inflammation in neutropenic mice with invasive aspergillosis (IA) that lack APN or the APN receptors AdipoR1 or AdipoR2. Alveolar macrophages (AMs), early immune sentinels that detect and respond to lung infection, express both receptors, and APN-deficient AMs exhibited an inflammatory phenotype that was associated with decreased fungal killing. Pharmacological stimulation of AMs with AdipoR agonist AdipoRon rescued deficient killing in APN-/- AMs and was dependent on the presence of either receptor. Finally, APN-enhanced fungal killing was associated with increased activation of the non-canonical LC3 pathway of autophagy. Thus, our study identifies a novel role for APN in LC3-mediated killing of A.fumigatus.
尽管固有免疫对于抵御人类机会性真菌病原体烟曲霉的抗真菌宿主防御至关重要，但必须控制潜在的有害炎症。脂联素（APN）是一种主要在脂肪组织中产生的脂肪因子，在肺等脂肪组织远端组织中发挥抗炎作用。我们观察到，缺乏APN或APN受体AdipoR1或AdipoR2的侵袭性曲霉病（IA）中性粒细胞减少小鼠的死亡率增加，真菌负荷和炎症增加。肺泡巨噬细胞（AMs）是检测和应对肺部感染的早期免疫哨兵，表达这两种受体，而缺乏APN的AMs表现出与真菌杀伤减少相关的炎症表型。用AdipoR激动剂AdipoRon对AMs进行药理刺激可挽救APN-/-AMs中缺陷的杀伤作用，且依赖于任一受体的存在。最后，APN增强的真菌杀伤与自噬非经典LC3途径的激活增加有关。因此，我们的研究确定了APN在LC3介导的烟曲霉杀伤中的新作用。
