Special Issue "An Evolutionary and Environmental Perspective of the Interaction of Nanomaterials with the Immune System-The Outcomes of the EU Project PANDORA"

A special issue of Nanomaterials (ISSN 2079-4991). This special issue belongs to the section "Biology and Medicines".

Deadline for manuscript submissions: closed (30 April 2021).

Special Issue Editor

Prof. Dr. Diana Boraschi
E-Mail Website
Guest Editor
Institute of Biochemistry and Cell Biology, National Research Council, 80131 Naples, Italy
Interests: Innate immunity; macrophages; adjuvants; innate memory; inflammation
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

We would like to take the occasion of the conclusion of the EU project PANDORA for making a summary of what we have learned regarding the interaction of engineered nanomaterials with the defensive systems of living organisms. PANDORA had the ambition of looking for common mechanisms of recognition and reaction, based on the high evolutionary conservation of innate immune mechanisms from plants to human beings. Whether nanomaterials could pose threats to the organisms’ integrity or whether immune defensive mechanisms can successfully deal with them is the question to which we have tried to respond. The PANDORA partners will provide their conclusions and opinions, based on the data they have generated, on the consequences of the interaction between nanomaterials and the innate immune system in their specific models’ organisms, spanning A. thaliana, terrestrial isopods, earthworms, mussels, sea urchins, and humans. Other colleagues, outside PANDORA, are warmly invited to contribute their view and help in completing the picture.

Prof. Dr. Diana Boraschi
Guest Editor

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Keywords

  • Engineered nanomaterials
  • Innate immunity
  • Environmental immuno-nanosafety
  • Human immuno-nanosafety
  • Evolution

Published Papers (8 papers)

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Research

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Article
Stressor-Dependant Changes in Immune Parameters in the Terrestrial Isopod Crustacean, Porcellio scaber: A Focus on Nanomaterials
Nanomaterials 2021, 11(4), 934; https://doi.org/10.3390/nano11040934 - 06 Apr 2021
Cited by 1 | Viewed by 561
Abstract
We compared the changes of selected immune parameters of Porcellio scaber to different stressors. The animals were either fed for two weeks with Au nanoparticles (NPs), CeO2 NPs, or Au ions or body-injected with Au NPs, CeO2 NPs, or lipopolysaccharide endotoxin. [...] Read more.
We compared the changes of selected immune parameters of Porcellio scaber to different stressors. The animals were either fed for two weeks with Au nanoparticles (NPs), CeO2 NPs, or Au ions or body-injected with Au NPs, CeO2 NPs, or lipopolysaccharide endotoxin. Contrary to expectations, the feeding experiment showed that both NPs caused a significant increase in the total haemocyte count (THC). In contrast, the ion-positive control resulted in a significantly decreased THC. Additionally, changes in phenoloxidase (PO)-like activity, haemocyte viability, and nitric oxide (NO) levels seemed to depend on the stressor. Injection experiments also showed stressor-dependant changes in measured parameters, such as CeO2 NPs and lipopolysaccharide endotoxin (LPS), caused more significant responses than Au NPs. These results show that feeding and injection of NPs caused an immune response and that the response differed significantly, depending on the exposure route. We did not expect the response to ingested NPs, due to the low exposure concentrations (100 μg/g dry weight food) and a firm gut epithelia, along with a lack of phagocytosis in the digestive system, which would theoretically prevent NPs from crossing the biological barrier. It remains a challenge for future research to reveal what the physiological and ecological significance is for the organism to sense and respond, via the immune system, to ingested foreign material. Full article
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Article
Primary and Memory Response of Human Monocytes to Vaccines: Role of Nanoparticulate Antigens in Inducing Innate Memory
Nanomaterials 2021, 11(4), 931; https://doi.org/10.3390/nano11040931 - 06 Apr 2021
Viewed by 598
Abstract
Innate immune cells such as monocytes and macrophages are activated in response to microbial and other challenges and mount an inflammatory defensive response. Exposed cells develop the so-called innate memory, which allows them to react differently to a subsequent challenge, aiming at better [...] Read more.
Innate immune cells such as monocytes and macrophages are activated in response to microbial and other challenges and mount an inflammatory defensive response. Exposed cells develop the so-called innate memory, which allows them to react differently to a subsequent challenge, aiming at better protection. In this study, using human primary monocytes in vitro, we have assessed the memory-inducing capacity of two antigenic molecules of Schistosoma mansoni in soluble form compared to the same molecules coupled to outer membrane vesicles of Neisseria lactamica. The results show that particulate challenges are much more efficient than soluble molecules in inducing innate memory, which is measured as the production of inflammatory and anti-inflammatory cytokines (TNFα, IL-6, IL-10). Controls run with LPS from Klebsiella pneumoniae compared to the whole bacteria show that while LPS alone has strong memory-inducing capacity, the entire bacteria are more efficient. These data suggest that microbial antigens that are unable to induce innate immune activation can nevertheless participate in innate activation and memory when in a particulate form, which is a notion that supports the use of nanoparticulate antigens in vaccination strategies for achieving adjuvant-like effects of innate activation as well as priming for improved reactivity to future challenges. Full article
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Article
Functional and Morphological Changes Induced in Mytilus Hemocytes by Selected Nanoparticles
Nanomaterials 2021, 11(2), 470; https://doi.org/10.3390/nano11020470 - 12 Feb 2021
Cited by 3 | Viewed by 717
Abstract
Nanoparticles (NPs) show various properties depending on their composition, size, and surface coating, which shape their interactions with biological systems. In particular, NPs have been shown to interact with immune cells, that represent a sensitive surveillance system of external and internal stimuli. In [...] Read more.
Nanoparticles (NPs) show various properties depending on their composition, size, and surface coating, which shape their interactions with biological systems. In particular, NPs have been shown to interact with immune cells, that represent a sensitive surveillance system of external and internal stimuli. In this light, in vitro models represent useful tools for investigating nano-bio-interactions in immune cells of different organisms, including invertebrates. In this work, the effects of selected types of NPs with different core composition, size and functionalization (custom-made PVP-AuNP and commercial nanopolystyrenes PS-NH2 and PS-COOH) were investigated in the hemocytes of the marine bivalve Mytilus galloprovincialis. The role of exposure medium was evaluated using either artificial seawater (ASW) or hemolymph serum (HS). Hemocyte morphology was investigated by scanning electron microscopy (SEM) and different functional parameters (lysosomal membrane stability, phagocytosis, and lysozyme release) were evaluated. The results show distinct morphological and functional changes induced in mussel hemocytes depending on the NP type and exposure medium. Mussel hemocytes may represent a powerful alternative in vitro model for a rapid pre-screening strategy for NPs, whose utilization will contribute to the understanding of the possible impact of environmental exposure to NPs in marine invertebrates. Full article
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Article
In Vitro Interactions of TiO2 Nanoparticles with Earthworm Coelomocytes: Immunotoxicity Assessment
Nanomaterials 2021, 11(1), 250; https://doi.org/10.3390/nano11010250 - 19 Jan 2021
Cited by 2 | Viewed by 1003
Abstract
Titanium dioxide nanoparticles (TiO2 NPs) are manufactured worldwide. Once they arrive in the soil environment, they can endanger living organisms. Hence, monitoring and assessing the effects of these nanoparticles is required. We focus on the Eisenia andrei earthworm immune cells exposed to [...] Read more.
Titanium dioxide nanoparticles (TiO2 NPs) are manufactured worldwide. Once they arrive in the soil environment, they can endanger living organisms. Hence, monitoring and assessing the effects of these nanoparticles is required. We focus on the Eisenia andrei earthworm immune cells exposed to sublethal concentrations of TiO2 NPs (1, 10, and 100 µg/mL) for 2, 6, and 24 h. TiO2 NPs at all concentrations did not affect cell viability. Further, TiO2 NPs did not cause changes in reactive oxygen species (ROS) production, malondialdehyde (MDA) production, and phagocytic activity. Similarly, they did not elicit DNA damage. Overall, we did not detect any toxic effects of TiO2 NPs at the cellular level. At the gene expression level, slight changes were detected. Metallothionein, fetidin/lysenin, lumbricin and MEK kinase I were upregulated in coelomocytes after exposure to 10 µg/mL TiO2 NPs for 6 h. Antioxidant enzyme expression was similar in exposed and control cells. TiO2 NPs were detected on coelomocyte membranes. However, our results do not show any strong effects of these nanoparticles on coelomocytes at both the cellular and molecular levels. Full article
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Article
An OMV-Based Nanovaccine Confers Safety and Protection against Pathogenic Escherichia coli via Both Humoral and Predominantly Th1 Immune Responses in Poultry
Nanomaterials 2020, 10(11), 2293; https://doi.org/10.3390/nano10112293 - 20 Nov 2020
Cited by 2 | Viewed by 688
Abstract
Avian pathogenic Escherichia coli (APEC) infection in poultry causes enormous economic losses and public health risks. Bacterial outer membrane vesicles (OMVs) and nano-sized proteolipids enriched with various immunogenic molecules have gained extensive interest as novel nanovaccines against bacterial infections. In this study, after [...] Read more.
Avian pathogenic Escherichia coli (APEC) infection in poultry causes enormous economic losses and public health risks. Bacterial outer membrane vesicles (OMVs) and nano-sized proteolipids enriched with various immunogenic molecules have gained extensive interest as novel nanovaccines against bacterial infections. In this study, after the preparation of APEC O2-derived OMVs (APEC_OMVs) using the ultracentrifugation method and characterization of them using electron microscopy and nanoparticle tracking analyses, we examined the safety and vaccination effect of APEC_OMVs in broiler chicks and investigated the underlying immunological mechanism of protection. The results showed that APEC_OMVs had membrane-enclosed structures with an average diameter of 89 nm. Vaccination with 50 μg of APEC_OMVs had no side effects and efficiently protected chicks against homologous infection. APEC_OMVs could be effectively taken up by chicken macrophages and activated innate immune responses in macrophages in vitro. APEC_OMV vaccination significantly improved activities of serum non-specific immune factors, enhanced the specific antibody response and promoted the proliferation of splenic and peripheral blood lymphocytes in response to mitogen. Furthermore, APEC_OMVs also elicited a predominantly IFN-γ-mediated Th1 response in splenic lymphocytes. Our data revealed the involvement of both non-specific immune responses and specific antibody and cytokine responses in the APEC_OMV-mediated protection, providing broader knowledge for the development of multivalent APEC_OMV-based nanovaccine with high safety and efficacy in the future. Full article
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Article
Safety Evaluation of TiO2 Nanoparticle-Based Sunscreen UV Filters on the Development and the Immunological State of the Sea Urchin Paracentrotus lividus
Nanomaterials 2020, 10(11), 2102; https://doi.org/10.3390/nano10112102 - 23 Oct 2020
Cited by 4 | Viewed by 1128
Abstract
Sunscreens are emulsions of water and oil that contain filters capable of protecting against the detrimental effects of ultraviolet radiation (UV). The widespread use of cosmetic products based on nanoparticulate UV filters has increased concerns regarding their safety and compatibility with both the [...] Read more.
Sunscreens are emulsions of water and oil that contain filters capable of protecting against the detrimental effects of ultraviolet radiation (UV). The widespread use of cosmetic products based on nanoparticulate UV filters has increased concerns regarding their safety and compatibility with both the environment and human health. In the present work, we evaluated the effects of titanium dioxide nanoparticle (TiO2 NP)-based UV filters with three different surface coatings on the development and immunity of the sea urchin, Paracentrotus lividus. A wide range of NP concentrations was analyzed, corresponding to different levels of dilution starting from the original cosmetic dispersion. Variations in surface coating, concentration, particle shape, and pre-dispersant medium (i.e., water or oil) influenced the embryonic development without producing a relevant developmental impairment. The most common embryonic abnormalities were related to the skeletal growth and the presence of a few cells, which were presumably involved in the particle uptake. Adult P. lividus immune cells exposed to silica-coated TiO2 NP-based filters showed a broad metabolic plasticity based on the biosynthesis of metabolites that mediate inflammation, phagocytosis, and antioxidant response. The results presented here highlight the biosafety of the TiO2 NP-based UV filters toward sea urchin, and the importance of developing safer-by-design sunscreens. Full article
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Article
The Effects of In Vivo Exposure to Copper Oxide Nanoparticles on the Gut Microbiome, Host Immunity, and Susceptibility to a Bacterial Infection in Earthworms
Nanomaterials 2020, 10(7), 1337; https://doi.org/10.3390/nano10071337 - 09 Jul 2020
Cited by 8 | Viewed by 1398
Abstract
Nanomaterials (NMs) can interact with the innate immunity of organisms. It remains, however, unclear whether these interactions can compromise the immune functioning of the host when faced with a disease threat. Co-exposure with pathogens is thus a powerful approach to assess the immuno-safety [...] Read more.
Nanomaterials (NMs) can interact with the innate immunity of organisms. It remains, however, unclear whether these interactions can compromise the immune functioning of the host when faced with a disease threat. Co-exposure with pathogens is thus a powerful approach to assess the immuno-safety of NMs. In this paper, we studied the impacts of in vivo exposure to a biocidal NM on the gut microbiome, host immune responses, and susceptibility of the host to a bacterial challenge in an earthworm. Eisenia fetida were exposed to CuO-nanoparticles in soil for 28 days, after which the earthworms were challenged with the soil bacterium Bacillus subtilis. Immune responses were monitored by measuring mRNA levels of known earthworm immune genes. Effects of treatments on the gut microbiome were also assessed to link microbiome changes to immune responses. Treatments caused a shift in the earthworm gut microbiome. Despite these effects, no impacts of treatment on the expression of earthworm immune markers were recorded. The methodological approach applied in this paper provides a useful framework for improved assessment of immuno-safety of NMs. In addition, we highlight the need to investigate time as a factor in earthworm immune responses to NM exposure. Full article
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Review

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Review
Cross-Species Comparisons of Nanoparticle Interactions with Innate Immune Systems: A Methodological Review
Nanomaterials 2021, 11(6), 1528; https://doi.org/10.3390/nano11061528 - 09 Jun 2021
Viewed by 803
Abstract
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 [...] Read more.
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. Full article
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