York Biomedical Research Institute, Hull York Medical School, University of York, York, United Kingdom.
Departments of Biology and Mathematics, University of York, York, United Kingdom.
Front Immunol. 2021 Dec 16;12:795554. doi: 10.3389/fimmu.2021.795554. eCollection 2021.
Increasing evidence suggests that in hosts infected with parasites of the complex, transmission of infection to the sand fly vector is linked to parasite repositories in the host skin. However, a detailed understanding of the dispersal (the mechanism of spread) and dispersion (the observed state of spread) of these obligatory-intracellular parasites and their host phagocytes in the skin is lacking. Using endogenously fluorescent parasites as a proxy, we apply image analysis combined with spatial point pattern models borrowed from ecology to characterize dispersion of parasitized myeloid cells (including Man and CD11c cells) and predict dispersal mechanisms in a previously described immunodeficient model of infection. Our results suggest that after initial seeding of infection in the skin, heavily parasite-infected myeloid cells are found in patches that resemble innate granulomas. Spread of parasites from these initial patches subsequently occurs through infection of recruited myeloid cells, ultimately leading to self-propagating networks of patch clusters. This combination of imaging and ecological pattern analysis to identify mechanisms driving the skin parasite landscape offers new perspectives on myeloid cell behavior following parasitism by and may also be applicable to elucidating the behavior of other intracellular tissue-resident pathogens and their host cells.
越来越多的证据表明，在感染复杂寄生虫的宿主中，寄生虫向沙蝇传播媒介的感染与宿主皮肤中的寄生虫储存库有关。然而，对于这些必需的细胞内寄生虫及其宿主吞噬细胞在皮肤中的扩散（传播机制）和分散（观察到的传播状态），我们还缺乏详细的了解。我们使用内源性荧光寄生虫作为替代物，应用图像分析并结合从生态学借来的空间点模式模型，来描述被寄生虫感染的髓样细胞（包括巨噬细胞和 CD11c 细胞）的分散，并预测在先前描述的免疫缺陷感染模型中寄生虫的扩散机制。我们的结果表明，在皮肤中感染初始定植后，富含寄生虫的髓样细胞以类似于天然肉芽肿的斑块形式出现。这些初始斑块中的寄生虫通过招募的髓样细胞感染传播，最终导致斑块集群的自我传播网络。这种将成像与生态模式分析相结合以确定驱动皮肤寄生虫景观的机制的方法，为寄生虫感染后髓样细胞行为提供了新的视角，也可能适用于阐明其他细胞内组织驻留病原体及其宿主细胞的行为。
