Neutrophils Mediate Maturation and Efflux of Lung Dendritic Cells in Response to Aspergillus fumigatus Germ Tubes
Neutrophils Mediate Maturation and Efflux of Lung Dendritic Cells in Response to Aspergillus fumigatus Germ Tubes
复制标题
DOI：
10.1128/iai.00097-12
复制
发表时间：
2012-05-01
影响因子：
3.1
通讯作者：
Mehrad, Borna
中科院分区：
文献类型：
--
作者：
Park, Stacy J.;Burdick, Marie D.;Mehrad, Borna
侵袭性曲霉病是中性粒细胞缺乏或功能障碍的一种危及生命的并发症。中性粒细胞减少症先前与表达cd11b的常规树突状细胞对曲霉菌种类的反应增强流入肺部有关，但中性粒细胞是否直接调节树突状细胞在这种感染中的功能尚不清楚。我们假设，在曲霉肺内攻击的情况下，中性粒细胞促进肺常规树突状细胞的成熟和运输，以引流纵隔淋巴结。我们报道中性粒细胞减少导致树突状细胞在曲霉攻击小鼠肺部的显著积累，但大大减少了它们独立于中性粒细胞杀微生物功能的纵隔淋巴结的出口。此外，中性粒细胞减少的动物的肺树突状细胞的表型比暴露于微生物的非中性粒细胞减少的小鼠更不成熟。与此一致的是，与中性粒细胞共孵生大大增强了体外暴露于曲霉的树突状细胞的共刺激分子的上调，这一过程依赖于细胞接触和树突状细胞受体DC-SIGN。综上所述，我们的数据支持在宿主对曲霉反应的背景下中性粒细胞和树突状细胞之间的免疫调节串扰，促进肺树突状细胞的成熟和外排。
Invasive aspergillosis is a life-threatening complication of neutrophil deficiency or dysfunction. Neutropenia has previously been associated with enhanced influx of CD11b-expressing conventional dendritic cells to the lungs in response to Aspergillus species, but whether neutrophils directly modulate the function of dendritic cells in this infection is not known. We hypothesized that, in the setting of intrapulmonary challenge with Aspergillus, neutrophils promote the maturation and traffic of lung conventional dendritic cells to draining mediastinal lymph nodes. We report that neutropenia results in a marked accumulation of dendritic cells in the lungs of mice challenged with Aspergillus but greatly diminishes their egress to mediastinal lymph nodes independent of neutrophil microbicidal functions. Furthermore, the phenotype of lung dendritic cells was more immature in neutropenic animals than in nonneutropenic mice exposed to the microorganism. Consistent with this, coincubation with neutrophils greatly enhanced the upregulation of costimulatory molecules on dendritic cells exposed to Aspergillus in vitro, a process that was dependent on cell contact and the dendritic cell receptor DC-SIGN. Taken together, our data support an immunomodulatory cross talk between neutrophils and dendritic cells in the context of host response to Aspergillus that promotes the maturation and efflux of lung dendritic cells.