Toolbox for In Vivo Imaging of Host–Parasite Interactions at Multiple Scales

Abstract

Animal models have for long been pivotal for parasitology research. Over the last few years, techniques such as intravital, optoacoustic and magnetic resonance imaging, optical projection tomography, and selective plane illumination microscopy developed promising potential for gaining insights into host-pathogen interactions by allowing different visualization forms in vivo and ex vivo. Advances including increased resolution, penetration depth, and acquisition speed, together with more complex image analysis methods facilitate tackling biological problems previously impossible to study and/or quantify. Here we discuss advances and challenges in the in vivo imaging toolbox, which hold important potential for the field of parasitology. KeywordsParasitology, imaging, in vivo, animal models Imaging toolbox in parasitologyImaging techniques developed for biomedical applications have had an important impact in parasitology research. Such techniques include platforms developed to image host-pathogen interactions at various scales, ranging from molecules to whole organisms (summarised in table 1). These techniques have complementary advantages with respect to each other. This review focuses on the technological advances used for visualization of host-pathogen interactions either in vivo, or ex vivo in whole organisms in five imaging techniques: intravital microscopy (IVM), optical projection tomography (OPT), bioluminescence imaging, optoacoustic imaging (OAI), and magnetic resonance imaging (MRI). Advanced fluorescence methods applied to intravital microscopyIntravital microscopy (IVM) is a powerful technique to investigate dynamic cellular processes and host-parasite interactions within functioning organs. Organs studied by IVM in the context of parasitology include the brain [1][2][3][4], the skin [5][6][7], the placenta [8,9], the lungs [10], the liver [11][12][13], and the spleen [14,15] (summarized in table 2, green=IVM exists; yellow=organ relevant but IVM never done; grey = IVM not done). Important advances in parasitology have been achieved using wide-field epifluorescence, confocal, spinning disc, or two-photon IVM.Recent developments, which have expanded the applications of IVM include the generation of

Three decades of listeriology through the prism of technological advances

“…Listeria has proved to be an invaluable model to study infection biology and develop original concepts in biology. New knowledge relied heavily on the design and use of innovative imaging and omics tools that irrigated listeriology and beyond, “the new microbiology.” Improved visualisation of native molecules, microorganisms and host cells in vitro and in tissular environments in the whole body provided new details on biological structures and on their organisation, functions and interactions (Baker, ; Bourdeau et al, ; Coombes & Robey, ; De Niz et al, ; Richter‐Dahlfors, Rhen, & Udekwu, ; Tainaka et al, ). Current combinations of cell imaging techniques with high spatio‐temporal resolution open breathtaking new avenues (Dersch & Graumann, ; Holden, ; Sahl et al, ).…”

3D imaging of undissected optically cleared Anopheles stephensi mosquitoes and midguts infected with Plasmodium parasites

“…During their life cycle, Plasmodium parasites adopt various forms, both invasive and replicative, within the vertebrate host and the mosquito vector (reviewed by [ 7 , 8 ]). While rodent-infecting parasites have been imaged in all relevant tissues within mice (skin, liver, blood and bone marrow) [ 9 – 12 ], imaging of parasites within the living mosquito has remained largely elusive and limited to the passive floating of sporozoites in the hemolymph and proboscis [ 13 , 14 ]. The development of sporozoites in vivo in the midgut and their entry into mosquito salivary glands remains to be visualized.…”

“…A pre-requisite for these imaging techniques applied to opaque samples is optical clearance, as in transparent media light propagates deeper into tissues, (reviewed by [ 15 ]. In order to generate a transparent sample, tissues can be chemically cleared using various solvents and imaging techniques (reviewed by [ 9 ]). After rendering the specimen transparent, OPT imaging is achieved via tissue trans- and epi-illumination over multiple projections [ 16 ] as the specimen is rotated through 360 degrees in angular steps around a single axis ( Fig 1C ).…”

Intravital microscopy: Imaging host–parasite interactions in lymphoid organs

“…Intravital microscopy (IVM) allows visualization of organs in living animals, down to subcellular resolution, to study cellular interactions, cell dynamics, motility, adhesion, rheology and anatomical changes in different tissue compartments through time. Major advances in imaging have allowed more organs, and a wider range of physiological phenomena, to be visualised in vivo (reviewed by De Niz et al, ). Among the most studied systems by IVM is the immune system (reviewed by Secklehner et al).…”