A sand fly salivary protein acts as a neutrophil chemoattractant.
A sand fly salivary protein acts as a neutrophil chemoattractant.
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DOI：
10.1038/s41467-021-23002-5
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发表时间：
2021-05-28
影响因子：
16.6
通讯作者：
Oliveira F
中科院分区：
文献类型：
--
作者：
Guimaraes-Costa AB;Shannon JP;Waclawiak I;Oliveira J;Meneses C;de Castro W;Wen X;Brzostowski J;Serafim TD;Andersen JF;Hickman HD;Kamhawi S;Valenzuela JG;Oliveira F
除了细菌甲酰肽或病毒趋化因子拟态之外，直接吸引哺乳动物先天细胞（例如中性粒细胞）的非脊椎动物或昆虫蛋白尚未得到分子特征。在这里，我们发现白蛉黄色唾液蛋白的成员在 Transwell 迁移或 EZ-TAXIScan 测定中诱导小鼠、犬和人类中性粒细胞的体外趋化性。我们使用流式细胞术和双光子活体显微镜在 Lysozyme-M-eGFP 转基因小鼠中证明了小鼠中性粒细胞的体内募集。我们确定这种约 45 kDa 的中性粒细胞趋化蛋白的结构与已知趋化因子的结构不同。这种化学引诱剂通过 G 蛋白偶联受体发挥作用，并且依赖于钙流入。重要的是，在与利什曼原虫共注射后，这种趋化蛋白增强了小鼠的病变病理学（P<0.0001）并增加了寄生虫负担（P<0.001），强调了白蛉唾液黄色蛋白对疾病结果的影响。这些发现表明，一些节肢动物载体衍生的因子，例如这种趋化唾液蛋白，激活而不是抑制宿主先天免疫反应，并且病原体利用这些炎症反应在宿主体内建立。细菌和病毒的趋化因子样部分已显示出免疫拟态。在这里，作者描述了一种诱导中性粒细胞趋化性的白蛉唾液蛋白，并探讨了其在寄生虫感染模型中的影响。
Apart from bacterial formyl peptides or viral chemokine mimicry, a non-vertebrate or insect protein that directly attracts mammalian innate cells such as neutrophils has not been molecularly characterized. Here, we show that members of sand fly yellow salivary proteins induce in vitro chemotaxis of mouse, canine and human neutrophils in transwell migration or EZ-TAXIScan assays. We demonstrate murine neutrophil recruitment in vivo using flow cytometry and two-photon intravital microscopy in Lysozyme-M-eGFP transgenic mice. We establish that the structure of this ~ 45 kDa neutrophil chemotactic protein does not resemble that of known chemokines. This chemoattractant acts through a G-protein-coupled receptor and is dependent on calcium influx. Of significance, this chemoattractant protein enhances lesion pathology (P < 0.0001) and increases parasite burden (P < 0.001) in mice upon co-injection with Leishmania parasites, underlining the impact of the sand fly salivary yellow proteins on disease outcome. These findings show that some arthropod vector-derived factors, such as this chemotactic salivary protein, activate rather than inhibit the host innate immune response, and that pathogens take advantage of these inflammatory responses to establish in the host. Immune mimicry has been shown in chemokine like moieties from bacteria and viruses. Here, the authors characterise a sand fly salivary protein that induces neutrophil chemotaxis and explore its impact in a model of parasitic infection.
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DOI：
10.1073/pnas.0802331105
发表时间：
2008-07-22
影响因子：
11.1
作者：
Kimblin, Nicola;Peters, Nathan;Sacks, David
通讯作者：
Sacks, David
影响因子：
17.1
作者：
Oliveira, Fabiano;Rowton, Edgar;Valenzuela, Jesus G.
通讯作者：
Valenzuela, Jesus G.
影响因子：
9.2
作者：
Nakatogawa, Shin-ichi;Oda, Yasunori;Hayakawa, Yoichi
通讯作者：
Hayakawa, Yoichi
影响因子：
2.8
作者：
Kato, Hirotomo;Jochim, Ryan C.;Valenzuela, Jesus G.
通讯作者：
Valenzuela, Jesus G.
影响因子：
64.8
作者：
Baggiolini, M
通讯作者：
Baggiolini, M