Inflammatory monocytes facilitate adaptive CD4 T cell responses during respiratory fungal infection.
Inflammatory monocytes facilitate adaptive CD4 T cell responses during respiratory fungal infection.
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DOI：
10.1016/j.chom.2009.10.007
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发表时间：
2009-11-19
影响因子：
30.3
通讯作者：
Pamer EG
中科院分区：
文献类型：
--
作者：
Hohl TM;Rivera A;Lipuma L;Gallegos A;Shi C;Mack M;Pamer EG
烟曲霉是一种普遍存在的真菌，可导致免疫功能低下的人发生侵袭性疾病。虽然单核细胞和抗原特异性CD4 T细胞有助于防御吸入的真菌孢子，但这些细胞在感染期间如何相互作用仍不清楚。研究炎症单核细胞和单核细胞衍生的树突状细胞在真菌感染中的作用，我们发现A。烟曲霉感染诱导表达趋化因子受体CCR2和Ly6C的炎性单核细胞流入肺和引流淋巴结。CCR2+细胞的耗竭减少了A.烟曲霉分生孢子从肺到引流淋巴结的运输，在呼吸激发后消除了CD4 T细胞的引发，并损害了肺真菌清除。相反，在全身性真菌感染期间CCR2+Ly6Chi单核细胞的消耗并不能阻止脾脏中的CD4 T细胞引发。我们的研究结果表明，肺CD4 T细胞对吸入孢子的反应需要CCR2+Ly6Chi单核细胞及其衍生物，揭示了这些细胞在适应性呼吸免疫反应中的区室限制功能。
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+Ly6Chi 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+Ly6Chi monocytes and their derivatives, revealing a compartmentally restricted function for these cells in adaptive respiratory immune responses.
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