Neutrophil derived LTB4 induces macrophage aggregation in response to encapsulated Streptococcus iniae infection.
Neutrophil derived LTB4 induces macrophage aggregation in response to encapsulated Streptococcus iniae infection.
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DOI：
10.1371/journal.pone.0179574
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Huttenlocher A
中科院分区：
文献类型：
--
作者：
Vincent WJB;Harvie EA;Sauer JD;Huttenlocher A
免疫细胞感知多种因素并对其做出反应，包括宿主和微生物来源的信号。了解细胞如何将这些线索转化为特定的细胞行为是一个复杂而关键的研究领域。我们以前已经表明，嗜中性粒细胞和巨噬细胞是重要的控制鱼类病原体海豚链球菌。在这里，我们报告了宿主和细菌的决定因素，导致形成有组织的巨噬细胞聚集体的一部分，在一个子集的感染幼虫的主机炎症反应。链球菌荚膜是聚集体形成所需的信号。巨噬细胞聚集与NFκB活性一致，这些聚集体的形成由中性粒细胞产生的白三烯B4（LTB 4）介导。催化LTB4合成最后一步的白三烯A4水解酶（Lta4h）的消耗、抑制或基因缺失导致巨噬细胞聚集的缺失。嗜中性粒细胞功能受损的淋巴细胞也有受损的巨噬细胞聚集，然而，聚集体的形成与外源性LTB4的加入部分获救。嗜中性粒细胞特异性表达lta4h足以拯救Lta4h缺陷型幼虫中的巨噬细胞聚集，并增加感染后的宿主存活率。总之，我们的研究结果强调了一种新的先天性免疫反应感染，其中特定的细菌产物驱动中性粒细胞，通过类花生酸信号调节巨噬细胞的行为。
Immune cells sense and react to a multitude of factors including both host and microbe-derived signals. Understanding how cells translate these cues into particular cellular behaviors is a complex yet critical area of study. We have previously shown that both neutrophils and macrophages are important for controlling the fish pathogen Streptococcus iniae. Here, we report both host and bacterial determinants leading to the formation of organized macrophage aggregates as part of the host inflammatory response in a subset of infected larvae. Streptococcal capsule was a required signal for aggregate formation. Macrophage aggregation coincided with NFκB activity, and the formation of these aggregates is mediated by leukotriene B4 (LTB4) produced by neutrophils. Depletion, inhibition, or genetic deletion of leukotriene A4 hydrolase (Lta4h), which catalyzes the last step in LTB4 synthesis, resulted in the absence of macrophage aggregation. Larvae with impaired neutrophil function also had impaired macrophage aggregation; however, aggregate formation was partially rescued with the addition of exogenous LTB4. Neutrophil-specific expression of lta4h was sufficient to rescue macrophage aggregation in Lta4h-deficient larvae and increased host survival following infection. In summary, our findings highlight a novel innate immune response to infection in which specific bacterial products drive neutrophils that modulate macrophage behavior through eicosanoid signaling.