Cross-talk in the innate immune system: Neutrophils instruct recruitment and activation of dendritic cells during microbial infection
Cross-talk in the innate immune system: Neutrophils instruct recruitment and activation of dendritic cells during microbial infection
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DOI：
10.4049/jimmunol.171.11.6052
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发表时间：
2003-12-01
影响因子：
4.4
通讯作者：
Denkers, EY
中科院分区：
文献类型：
--
作者：
Bennouna, S;Bliss, SK;Denkers, EY
I型炎症细胞因子对许多微生物病原体（包括刚地弓形虫）的免疫至关重要。树突状细胞（DC）是启动I型免疫的关键，但中性粒细胞也是参与Th1反应启动的趋化因子和细胞因子的来源。我们发现刚地弓形虫触发中性粒细胞合成CC趋化因子配体（CCL）3、CCL4、CCL5和CCL20，这些趋化因子对未成熟DC具有强烈的趋化作用。此外，从寄生虫刺激的多形核白细胞获得的上清液诱导DC产生白细胞介素 - 12（p40）和肿瘤坏死因子 - α。寄生虫触发的中性粒细胞还释放诱导DC CD40和CD86上调的因子，并且这种反应依赖于寄生虫触发的中性粒细胞肿瘤坏死因子 - α的产生。通过检查中性粒细胞耗竭小鼠感染后脾脏DC细胞因子的产生，获得了多形核白细胞对DC激活具有重要影响的体内证据。如体外流式细胞术分析和体外培养试验所示，这些动物脾脏DC白细胞介素 - 12和肿瘤坏死因子 - α的产生严重减少。我们的结果揭示了在微生物感染期间中性粒细胞在DC功能中先前未被认识到的调节作用，并表明这些细胞群之间的相互作用是对感染的先天免疫反应的一个重要组成部分。
Type I inflammatory cytokines are essential for immunity to many microbial pathogens, including Toxoplasma gondii. Dendritic cells (DC) are key to initiating type 1 immunity, but neutrophils are also a source of chemokines and cytokines involved in Th1 response ignition. We found that T. gondii triggered neutrophil synthesis of CC chemokine ligand (CCL)3, CCL4, CCL5, and CCL20, chemokines that were strongly chemotactic for immature DC. Moreover, supernatants obtained from parasite-stimulated polymorphonuclear leukocytes induced DC IL-12(p40) and TNF-alpha production. Parasite-triggered neutrophils also released factors that induced DC CD40 and CD86 up-regulation, and this response was dependent upon parasite-triggered neutrophil TNF-alpha production. In vivo evidence that polymorphonuclear leukocytes exert an important influence on DC activation was obtained by examining splenic DC cytokine production following infection of neutrophil-depleted mice. These animals displayed severely curtailed splenic DC IL-12 and TNF-alpha production, as revealed by ex vivo flow cytometric analysis and in vitro culture assay. Our results reveal a previously unrecognized regulatory role for neutrophils in DC function during microbial infection, and suggest that cross-talk between these cell populations is an important component of the innate immune response to infection.