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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 innate immune system evolved to detect and react against potential dangers such as bacteria, viruses, and environmental particles. The advent of modern technology has exposed innate immune cells, such as monocytes, macrophages, and dendritic cells, to a relatively novel type of particulate matter, i.e., engineered nanoparticles. Nanoparticles are not inherently pathogenic, and yet cases have been described in which specific nanoparticle types can either induce innate/inflammatory responses or modulate the activity of activated innate cells. Many of these studies rely upon activation by agonists of toll-like receptors, such as lipopolysaccharide or peptidoglycan, instead of the more realistic stimulation by whole live organisms. In this review we examine and discuss the effects of nanoparticles on innate immune cells activated by live bacteria. We focus in particular on how nanoparticles may interfere with bacterial processes in the context of innate activation, and confine our scope to the effects due to particles themselves, rather than to molecules adsorbed on the particle surface. Finally, we examine the long-lasting consequences of coexposure to nanoparticles and bacteria, in terms of potential microbiome alterations and innate immune memory, and address nanoparticle-based vaccine strategies against bacterial infection.

The innate immune system evolved to detect and react against potential dangers such as bacteria, viruses, and environmental particles. The advent of modern technology has exposed innate immune cells, such as monocytes, macrophages, and dendritic cells, to a relatively novel type of particulate matter, i.e., engineered nanoparticles. Nanoparticles are not inherently pathogenic, and yet cases have been described in which specific nanoparticle types can either induce innate/inflammatory responses or modulate the activity of activated innate cells. Many of these studies rely upon activation by agonists of toll-like receptors, such as lipopolysaccharide or peptidoglycan, instead of the more realistic stimulation by whole live organisms. In this review we examine and discuss the effects of nanoparticles on innate immune cells activated by live bacteria. We focus in particular on how nanoparticles may interfere with bacterial processes in the context of innate activation, and confine our scope to the effects due to particles themselves, rather than to molecules adsorbed on the particle surface. Finally, we examine the long-lasting consequences of coexposure to nanoparticles and bacteria, in terms of potential microbiome alterations and innate immune memory, and address nanoparticle-based vaccine strategies against bacterial infection.

Metal nanomaterials are increasingly applied as an antimicrobial agent in consumer products, coatings and pesticides. Through environmental release, non-target microbes, including symbiotic microbiota associated with animals, may be at risk due to exposure to these nanomaterials. Here, the effects of biocidal nanomaterial exposures (i.e. copper oxide and silver) on the gut microbiome of three earthworm species (i.e. Eisenia fetida, Lumbricus terrestris and Aporrectodea calignosa) and associated soils are studied using a metabarcoding approach. Further, the consequences of a microbiome disruption by nanomaterials on the E. fetida immune responses and the resilience of E. fetida to an infection by the bacterium Bacillus subtilis are investigated. This thesis provides a unique and in-depth view of the gut bacterial microbiome of three environmentally relevant earthworm species and shows how metal pollutants can affect these host-associated bacterial communities. It is shown that the resident component of the earthworm gut microbiome is largely independent from the associated soil bacterial communities. Further, through high replication (within and across concentrations), this thesis shows that the earthworm resident gut microbiome is largely resilient to exposure to antimicrobial nanomaterials. However, a key earthworm symbiont (i.e. the Mollicutes ‘Candidatus Lumbricincola’) that likely plays a role in earthworm digestion is negatively affected by exposure to copper oxide nanomaterial. These adverse effects on this symbiont were recorded in both short-term lab exposures and long-term outdoor soil mesocosm studies. Despite the impact of copper oxide nanomaterial on the earthworm gut microbiome, no evidence for an effect of nanomaterial exposure on host immunity or host susceptibility to a bacterial infection was found. This thesis demonstrates that pollutants can adversely affect crucial earthworm microbes, highlighting the need for further testing for effects of pollutants on microbiomes. The methodological approach adopted in this thesis should guide such future studies.