Early NK cell-derived IFN-{gamma} is essential to host defense in neutropenic invasive aspergillosis.
Early NK cell-derived IFN-{gamma} is essential to host defense in neutropenic invasive aspergillosis.
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DOI：
10.4049/jimmunol.0803462
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发表时间：
2009-04-01
期刊：
影响因子：
--
通讯作者：
Mehrad B
中科院分区：
文献类型：
--
作者：
Park SJ;Hughes MA;Burdick M;Strieter RM;Mehrad B
侵袭性曲霉病是最常见的人类真菌感染之一，发生在免疫反应严重且复杂的缺陷的患者中。此前已发现自然杀伤细胞在宿主防御这种感染方面发挥着重要作用，但这种作用的机制尚不清楚。我们假设 NK 细胞通过在早期感染期间充当 IFN-γ 的主要来源来介导其对侵袭性曲霉病的保护作用。我们发现，在患有侵袭性曲霉病的中性粒细胞减少小鼠的肺部，NK细胞是早期感染期间能够产生IFN-γ的主要细胞群。 NK 细胞的耗竭导致肺 IFN-γ 水平降低，肺部真菌负荷增加，且与 T 和 B 细胞亚群无关。 NK 细胞的消耗和 IFN-γ 的缺乏导致感染易感性的类似增加，但 IFN-γ 缺陷宿主中 NK 细胞的消耗并没有导致感染严重程度的进一步增加。 NK 细胞衍生的 IFN-γ 在体外引起巨噬细胞抗菌作用增强，并导致肺部 IFN 诱导趋化因子的表达增加。最后，从野生型而非缺乏 IFN-γ 的宿主转移活化的 NK 细胞，导致 IFN-γ 缺乏和野生型受体的肺部病原体清除率更高。综上所述，这些数据表明 NK 细胞是中性粒细胞减少性侵袭性曲霉病肺部早期 IFN-γ 的主要来源，这是防御这种感染的重要机制。
Invasive aspergillosis is among the most common human fungal infections and occurs in patients with severe and complex defects in immune responses. Natural killer cells have previously been found to be important in host defense against this infection, but the mechanism of this effect is not known. We hypothesized that NK cells mediate their protective effect in invasive aspergillosis by acting as the major source of IFN-γ during early infection. We found that, in the lungs of neutropenic mice with invasive aspergillosis, NK cells were the major population of cells capable of generating IFN-γ during early infection. Depletion of NK cells resulted in reduced lung IFN-γ levels and increased lung fungal load that was independent of T and B cell subsets. Depletion of NK cells and absence of IFN-γ resulted in a similar increase in susceptibility to the infection, but depletion of NK cells in IFN-γ-deficient hosts did not result in further increase in severity of the infection. NK cell-derived IFN-γ caused enhanced macrophage antimicrobial effects in vitro and also resulted in greater expression of IFN-inducible chemokines in the lungs. Finally, transfer of activated NK cells from wildtype, but not IFN-γ-deficient hosts, resulted in greater pathogen clearance from the lungs of both IFN-γ-deficient and wildtype recipients. Taken together, these data indicate that NK cells are the main source of early IFN-γ in the lungs in neutropenic invasive aspergillosis, and this is an important mechanism in the defense against this infection.
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影响因子：
3.1
作者：
Brieland, JK;Jackson, C;O'Garra, A
通讯作者：
O'Garra, A
DOI：
10.1084/jem.184.3.963
发表时间：
1996-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Loetscher M;Gerber B;Loetscher P;Jones SA;Piali L;Clark-Lewis I;Baggiolini M;Moser B
通讯作者：
Moser B
影响因子：
6.4
作者：
Cenci, E;Mencacci, A;Romani, L
通讯作者：
Romani, L
影响因子：
6.4
作者：
Grazziutti, ML;Rex, JH;Savary, CA
通讯作者：
Savary, CA
影响因子：
6.4
作者：
Cenci, E;Mencacci, A;Romani, L
通讯作者：
Romani, L