Infectious Disease Service, Department of Medicine, and Immunology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Cell Host Microbe. 2009 Nov 19;6(5):470-81. doi: 10.1016/j.chom.2009.10.007.
Aspergillus fumigatus, a ubiquitous fungus, causes invasive disease in immunocompromised humans. Although monocytes and antigen-specific CD4 T cells contribute to defense against inhaled fungal spores, how these cells interact during infection remains undefined. Investigating the role of inflammatory monocytes and monocyte-derived dendritic cells during fungal infection, we find that A. fumigatus infection induces an influx of chemokine receptor CCR2- and Ly6C-expressing inflammatory monocytes into lungs and draining lymph nodes. Depletion of CCR2(+) cells reduced A. fumigatus conidial transport from lungs to draining lymph nodes, abolished CD4 T cell priming following respiratory challenge, and impaired pulmonary fungal clearance. In contrast, depletion of CCR2(+)Ly6C(hi) monocytes during systemic fungal infection did not prevent CD4 T cell priming in the spleen. Our findings demonstrate that pulmonary CD4 T cell responses to inhaled spores require CCR2(+)Ly6C(hi) monocytes and their derivatives, revealing a compartmentally restricted function for these cells in adaptive respiratory immune responses.
烟曲霉是一种无处不在的真菌，可导致免疫功能低下的人体发生侵袭性疾病。虽然单核细胞和抗原特异性 CD4 T 细胞有助于抵御吸入的真菌孢子，但这些细胞在感染过程中的相互作用尚不清楚。在研究真菌感染期间炎症性单核细胞和单核细胞衍生的树突状细胞的作用时，我们发现烟曲霉感染会诱导趋化因子受体 CCR2 和 Ly6C 表达的炎症性单核细胞涌入肺部和引流淋巴结。CCR2(+)细胞耗竭会减少烟曲霉分生孢子从肺部向引流淋巴结的转移，消除呼吸道挑战后的 CD4 T 细胞启动，并损害肺部真菌清除。相比之下，在系统性真菌感染期间耗竭 CCR2(+)Ly6C(hi)单核细胞不会阻止脾脏中 CD4 T 细胞的启动。我们的研究结果表明，肺部对吸入孢子的 CD4 T 细胞反应需要 CCR2(+)Ly6C(hi)单核细胞及其衍生物，这揭示了这些细胞在适应性呼吸免疫反应中具有局部受限的功能。
