Characterization of spatial lipidomic signatures in tick-bitten guinea pig skin as a model for host-vector-pathogen interaction profiling.

Characterization of spatial lipidomic signatures in tick-bitten guinea pig skin as a model for host-vector-pathogen interaction profiling.
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DOI:
10.1128/msystems.00927-23
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发表时间:
2023-12-21
期刊:
影响因子:
6.4
通讯作者:
--
中科院分区:
生物学2区
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--
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空间感知的从头发现方法是在复杂的门间相互作用,如节肢动物和哺乳动物的治疗目标识别的重要工具。值得注意的是,这些方法在理想情况下应该是物种不可知的,显示所有相互作用物种的独特特征。我们评估了基质辅助解吸/电离质谱成像(MALDI-MSI,这里简称为MSI)作为一个空间的“组学”方法,同时配置文件的节肢动物载体(硬蜱)和哺乳动物皮肤(豚鼠)在咬模型的可能性。我们证明了MSI的可行性,使用明胶稳定的样品安装,允许连续切片和映射脂质控制和叮咬的皮肤,包括蜱体和嵌入式口器。我们确定了独特的脂质离子模式,并观察到与组织学变化相一致的咬合部位下的脂质重组。此外,在蜱虫体内观察到几种离子,在真皮和对照皮肤中强度较低,表明脂质从蜱虫传输到哺乳动物皮肤。这些结果建立了一个多系统的方法,发现跨物种的分子相互作用,可以进一步发展为目标,破坏载体-宿主界面。在这里,我们展示了适应性的空间“组学”的方法,以确定在媒介-宿主界面的蜱在哺乳动物血餐调节的门间过程。这种方法能够更好地理解宿主,节肢动物载体和传播的病原体之间复杂的二分或三分分子相互作用,并有助于空间感知治疗靶点的发现和描述的发展。
Spatially aware de novo discovery methods are essential tools for therapeutic target identification in complex interphylum interactions such as arthropods and mammals. Notably, the methods should ideally be species agnostic, showing unique features of all interacting species. We evaluated the possibilities for matrix-assisted desorption/ionization mass spectrometry imaging (MALDI-MSI, referred to here as MSI) as a spatial “omics” method to simultaneously profile both an arthropod vector (Ixodes tick) and a mammalian skin (guinea pig) in a bite model. We demonstrated the feasibility of MSI using gelatin-stabilized sample mounting that allowed for serial sectioning and mapping lipids in control and bitten skin, including the tick body and embedded mouthparts. We identified unique lipid ion patterns and observed lipid reorganization beneath the bite site consistent with histological changes. Furthermore, several ions were observed in the tick body with lower intensity in the dermis and control skin, suggesting the transmission of lipids from the tick to mammalian skin. These results establish a multi-system approach for discovering cross-species molecular interactions that can be further developed as targets to disrupt the vector-host interface. Here, we demonstrate the adaptability of spatial “omics” methods to identify interphylum processes regulated at the vector-host interface of ticks during a mammalian blood meal. This approach enables a better understanding of complex bipartite or tripartite molecular interactions between hosts, arthropod vectors and transmitted pathogens, and contributes toward the development of spatially aware therapeutic target discovery and description.
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