Neutropenia enhances lung dendritic cell recruitment in response to Aspergillus via a cytokine-to-chemokine amplification loop.
Neutropenia enhances lung dendritic cell recruitment in response to Aspergillus via a cytokine-to-chemokine amplification loop.
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DOI：
10.4049/jimmunol.1002064
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发表时间：
2010-11-15
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;Burdick MD;Brix WK;Stoler MH;Askew DS;Strieter RM;Mehrad B
目前对中性粒细胞减少感染背景下特定防御机制的了解有限。以前有报道说，侵袭性曲霉病，一种典型的机会性感染，在贫血的主机，是与显着的积累，炎性树突状细胞（DC）在肺部。鉴于最近的数据表明，中性粒细胞可以调节免疫反应独立于其直接的微生物杀伤，我们假设，中性粒细胞减少症的影响，确定肺树突状细胞的迁移和表型的宿主对曲霉菌的反应。发现炎性DC，而不是其他DC亚群，在用杀死的或活的减毒曲霉菌攻击的贫血宿主的肺中积累，与非贫血宿主相比，表明这种积累不依赖于嗜中性粒细胞杀微生物活性。发现在血小板减少宿主中这种积累的机制是增加了DC或其前体从血液到肺的流入。这种效应归因于与非血小板减少动物相比，血小板减少动物的肺TNF表达大大升高。这导致趋化因子配体CCL2和CCL20的更大的肺表达，其反过来介导产生TNF的炎性DC的增强的募集，从而导致正反馈循环。最后，在血小板减少型侵袭性曲霉病的背景下，DCs的耗竭导致真菌清除受损，表明这种机制对宿主具有保护作用。这些观察结果确定了一种新的防御机制，在侵袭性曲霉菌病，是在DC交通和表型的改变的结果，是特定于血小板减少的主机。
Current understanding of specific defense mechanisms in the context of neutropenic infections is limited. It has previously been reported that invasive aspergillosis, a prototypic opportunistic infection in neutropenic hosts, is associated with marked accumulation of inflammatory dendritic cells (DCs) in the lungs. Given recent data indicating that neutrophils can modulate immune responses independent of their direct microbial killing, we hypothesized that neutropenia impacts the host response to Aspergillus by determining the migration and phenotype of lung DCs. Inflammatory DCs, but not other DC subsets, were found to accumulate in the lungs of neutropenic hosts challenged with killed or live-attenuated Aspergillus as compared to non-neutropenic hosts, indicating that the accumulation was independent of neutrophil microbicidal activity. The mechanism of this accumulation in neutropenic hosts was found to be augmented influx of DCs, or their precursors, from the blood to the lungs. This effect was attributable to greatly elevated lung TNF expression in neutropenic as compared to non-neutropenic animals. This resulted in greater lung expression of the chemokine ligands CCL2 and CCL20 which, in turn, mediated enhanced recruitment of TNF-producing inflammatory DCs resulting in a positive-feedback cycle. Finally, in the context of neutropenic invasive aspergillosis, depletion of DCs resulted in impaired fungal clearance, indicating that this mechanism is protective for the host. These observations identify a novel defense mechanism in invasive aspergillosis that is the result of alterations in DC traffic and phenotype and is specific to neutropenic hosts.
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影响因子：
30.3
作者：
Hohl TM;Rivera A;Lipuma L;Gallegos A;Shi C;Mack M;Pamer EG
通讯作者：
Pamer EG
人类嗜中性粒细胞衍生的组织蛋白酶G和Azurocidin/cap37鉴定为单核细胞和中性粒细胞的趋化剂。
DOI：
10.1084/jem.186.5.739
发表时间：
1997-08-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chertov O;Ueda H;Xu LL;Tani K;Murphy WJ;Wang JM;Howard OM;Sayers TJ;Oppenheim JJ
通讯作者：
Oppenheim JJ
影响因子：
32.4
作者：
Jung, S;Unutmaz, D;Lang, RA
通讯作者：
Lang, RA
影响因子：
4.4
作者：
De la Rosa, Gonzalo;Yang, De;Oppenheim, Joost J.
通讯作者：
Oppenheim, Joost J.
影响因子：
4.4
作者：
Bennouna, S;Bliss, SK;Denkers, EY
通讯作者：
Denkers, EY