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Many components of the innate immune system are evolutionarily conserved and shared across many living organisms, from plants and invertebrates to humans. Therefore, these shared features can allow the comparative study of potentially dangerous substances, such as engineered nanoparticles (NPs). However, differences of methodology and procedure between diverse species and models make comparison of innate immune responses to NPs between organisms difficult in many cases. To this aim, this review provides an overview of suitable methods and assays that can be used to measure NP immune interactions across species in a multidisciplinary approach. The first part of this review describes the main innate immune defense characteristics of the selected models that can be associated to NPs exposure. In the second part, the different modes of exposure to NPs across models (considering isolated cells or whole organisms) and the main endpoints measured are discussed. In this synergistic perspective, we provide an overview of the current state of important cross-disciplinary immunological models to study NP-immune interactions and identify future research needs. As such, this paper could be used as a methodological reference point for future nano-immunosafety studies. All authors were supported by the EU H2020 project PANDORA, grant number 671881.

The particulate nature of nanoparticles (NPs) dictates a preferential interaction with \ud cells of the immune system assigned to recognition and elimination of foreign \ud particulates. Probing safety of nano-objects by defining immune responses of \ud environmental organisms is therefore key to environmental nanosafety. Earthworms \ud represent major immunosafety models representing keystone ecosystem engineers and \ud being in intimate contact with soils ensuring exposure to terrestrial NPs. Innate \ud immunity represents the first line of defence against pathogens in invertebrates and \ud despite extensive description of cell populations involved a dearth of information about \ud the associated molecular components exists. This thesis aimed to use genomics \ud approaches to generate a comprehensive systems immunity description of earthworm \ud prior to exploiting transcriptomics to explore the interaction of NPs and earthworms.\ud A tissue-specific transcriptomic atlas has been established for Eisenia fetida and Eisenia \ud andrei representing six tissues from each species. The resultant comparative \ud transcriptomic resource represented an innate immunity database containing immune-related genes from major immune signalling pathways. To refine the tissue-specific \ud database we generated a de novo genome for E. fetida with high contiguity and \ud completeness. Finally, to enhance insight into the different immune functions of the \ud individual types of coelomocytes we generated transcriptomic datasets from eleocytes, \ud hyaline and granular amoebocytes.\ud The interaction between NPs and the earthworm immune system was then explored by \ud combining the direct introduction of copper oxide NPs with bacterial challenge and \ud following the transcript changes within individual coelomocytes cell populations. This \ud resolved the spatial-temporal impact on the immune system into three distinct phases: \ud direct, systemic and differentiation responses. A complementary soil-based exposure \ud using a range of CuNPs, Silicon-CuNPs and copper ion doses explored the comparative \ud response after soil-based biotransformation. This revealed Si-CuNPs to elicit a negligible \ud response whilst differentially regulated genes under high CuNPs were distinct from \ud equivalent copper ion exposure the pathways impacted intersected substantially.