Aspergillus fumigatus, a ubiquitous mold, is a common cause of invasive aspergillosis (IA) in immunocompromised patients. Host defense against IA relies on lung-infiltrating neutrophils and monocyte-derived dendritic cells (Mo-DCs). Here, we demonstrate that plasmacytoid dendritic cells (pDCs), which are prototypically antiviral cells, participate in innate immune crosstalk underlying mucosal antifungal immunity. Aspergillus-infected murine Mo-DCs and neutrophils recruited pDCs to the lung by releasing the CXCR3 ligands, CXCL9 and CXCL10, in a Dectin-1 and Card9- and type I and III interferon signaling-dependent manner, respectively. During aspergillosis, circulating pDCs entered the lung in response to CXCR3-dependent signals. Via targeted pDC ablation, we found that pDCs were essential for host defense in the presence of normal neutrophil and Mo-DC numbers. Although interactions between pDC and fungal cells were not detected, pDCs regulated neutrophil NADPH oxidase activity and conidial killing. Thus, pDCs act as positive feedback amplifiers of neutrophil effector activity against inhaled mold conidia.

烟曲霉是一种无处不在的霉菌，是免疫功能低下患者侵袭性曲霉病 (IA) 的常见原因。宿主对 IA 的防御依赖于肺浸润性中性粒细胞和单核细胞衍生的树突状细胞 (Mo-DC)。在这里，我们证明浆细胞样树突状细胞 (pDC) 是典型的抗病毒细胞，参与粘膜抗真菌免疫的先天免疫串扰。曲霉属-感染的小鼠 Mo-DC 和嗜中性粒细胞分别以 Dectin-1 和 Card9 以及 I 型和 III 型干扰素信号依赖性方式释放 CXCR3 配体 CXCL9 和 CXCL10，从而将 pDC 募集到肺部。在曲霉病期间，循环 pDC 响应 CXCR3 依赖性信号进入肺部。通过靶向 pDC 消融，我们发现 pDC 在存在正常中性粒细胞和 Mo-DC 数量的情况下对于宿主防御至关重要。尽管未检测到 pDC 与真菌细胞之间的相互作用，但 pDC 调节中性粒细胞 NADPH 氧化酶活性和分生孢子杀灭。因此，pDC 作为中性粒细胞效应器活性对吸入霉菌分生孢子的正反馈放大器。