Essential role for neutrophils but not alveolar macrophages at early time points following Aspergillus fumigatus infection.
Essential role for neutrophils but not alveolar macrophages at early time points following Aspergillus fumigatus infection.
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DOI：
10.1086/600380
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发表时间：
2009-08-15
期刊：
影响因子：
--
通讯作者：
Hohl TM
中科院分区：
文献类型：
--
作者：
Mircescu MM;Lipuma L;van Rooijen N;Pamer EG;Hohl TM
肺泡巨噬细胞和中性粒细胞介导针对机会性真菌病原体烟曲霉的先天免疫防御，并且被认为是吸入真菌孢子（分生孢子）后宿主存活所必需的。虽然肺泡巨噬细胞被假定为杀死吸入的分生孢子和中性粒细胞被认为是对菌丝的作用，肺泡巨噬细胞和中性粒细胞对A.烟曲霉仍然没有完全定义。为了更精确地表征肺泡巨噬细胞和中性粒细胞在抗真菌宿主防御中的贡献，我们在分生孢子肺攻击后的不同时间选择性地耗尽每个细胞群体。小鼠在肺部A.烟曲霉感染可正常募集中性粒细胞，限制菌丝组织侵入。相反，感染前或感染后3小时内的中性粒细胞耗竭与高死亡率相关。然而，在较晚的时间点，中性粒细胞耗竭与几乎正常的生存率相关。我们的研究表明，中性粒细胞，而不是肺泡巨噬细胞，提供必要的抗分生孢子防御，并在呼吸树的短期内涌入足以防止分生孢子萌发和侵入性疾病。
Alveolar macrophages and neutrophils mediate innate immune defense against the opportunistic fungal pathogen Aspergillus fumigatus and are believed to be essential for host survival following inhalation of fungal spores (conidia). Although alveolar macrophages are postulated to kill inhaled conidia and neutrophils are believed to act against hyphae, the relative contribution of alveolar macrophages and neutrophils to early defense against A. fumigatus remain incompletely defined. To more precisely characterize the contributions of alveolar macrophages and neutrophils in antifungal host defense, we selectively depleted each cell population at different times following pulmonary challenge with conidia. Mice depleted of alveolar macrophages prior to pulmonary A. fumigatus infection recruited neutrophils normally and restricted hyphal tissue invasion. In contrast, neutrophil depletion prior to or within 3 h after infection was associated with high mortality. Neutrophil depletion at later time points, however, was associated with nearly normal survival rates. Our studies suggest that neutrophils, but not alveolar macrophages, provide essential anticonidial defense and that a brief period of influx into the respiratory tree is sufficient to prevent conidial germination and invasive disease.
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