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) | Viewed by 45685

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor


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, Collections and Topics 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

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nanomaterials is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

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

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (11 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review

3 pages, 185 KiB  
Editorial
An Evolutionary and Environmental Perspective of the Interaction of Nanomaterials with the Immune System
by Diana Boraschi
Nanomaterials 2022, 12(6), 957; https://doi.org/10.3390/nano12060957 - 14 Mar 2022
Viewed by 1499
Abstract
Assessing the modes of interaction between engineered nanomaterials and the immune system is a topic of particular interest for research in several fields, from a toxicological and safety perspective to potential nano-based immunomodulatory strategies for medical use [...] Full article

Research

Jump to: Editorial, Review

24 pages, 2680 KiB  
Article
Growth-Promoting Gold Nanoparticles Decrease Stress Responses in Arabidopsis Seedlings
by Eleonora Ferrari, Francesco Barbero, Marti Busquets-Fité, Mirita Franz-Wachtel, Heinz-R. Köhler, Victor Puntes and Birgit Kemmerling
Nanomaterials 2021, 11(12), 3161; https://doi.org/10.3390/nano11123161 - 23 Nov 2021
Cited by 31 | Viewed by 3380
Abstract
The global economic success of man-made nanoscale materials has led to a higher production rate and diversification of emission sources in the environment. For these reasons, novel nanosafety approaches to assess the environmental impact of engineered nanomaterials are required. While studying the potential [...] Read more.
The global economic success of man-made nanoscale materials has led to a higher production rate and diversification of emission sources in the environment. For these reasons, novel nanosafety approaches to assess the environmental impact of engineered nanomaterials are required. While studying the potential toxicity of metal nanoparticles (NPs), we realized that gold nanoparticles (AuNPs) have a growth-promoting rather than a stress-inducing effect. In this study we established stable short- and long-term exposition systems for testing plant responses to NPs. Exposure of plants to moderate concentrations of AuNPs resulted in enhanced growth of the plants with longer primary roots, more and longer lateral roots and increased rosette diameter, and reduced oxidative stress responses elicited by the immune-stimulatory PAMP flg22. Our data did not reveal any detrimental effects of AuNPs on plants but clearly showed positive effects on growth, presumably by their protective influence on oxidative stress responses. Differential transcriptomics and proteomics analyses revealed that oxidative stress responses are downregulated whereas growth-promoting genes/proteins are upregulated. These omics datasets after AuNP exposure can now be exploited to study the underlying molecular mechanisms of AuNP-induced growth-promotion. Full article
Show Figures

Figure 1

18 pages, 13686 KiB  
Article
Stressor-Dependant Changes in Immune Parameters in the Terrestrial Isopod Crustacean, Porcellio scaber: A Focus on Nanomaterials
by Craig Mayall, Andraz Dolar, Anita Jemec Kokalj, Sara Novak, Jaka Razinger, Francesco Barbero, Victor Puntes and Damjana Drobne
Nanomaterials 2021, 11(4), 934; https://doi.org/10.3390/nano11040934 - 6 Apr 2021
Cited by 11 | Viewed by 3109
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
Show Figures

Figure 1

16 pages, 2027 KiB  
Article
Primary and Memory Response of Human Monocytes to Vaccines: Role of Nanoparticulate Antigens in Inducing Innate Memory
by Mayra M. Ferrari Barbosa, Alex Issamu Kanno, Leonardo Paiva Farias, Mariusz Madej, Gergö Sipos, Silverio Sbrana, Luigina Romani, Diana Boraschi, Luciana C. C. Leite and Paola Italiani
Nanomaterials 2021, 11(4), 931; https://doi.org/10.3390/nano11040931 - 6 Apr 2021
Cited by 5 | Viewed by 2979
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
Show Figures

Figure 1

16 pages, 8167 KiB  
Article
Functional and Morphological Changes Induced in Mytilus Hemocytes by Selected Nanoparticles
by Manon Auguste, Craig Mayall, Francesco Barbero, Matej Hočevar, Stefano Alberti, Giacomo Grassi, Victor F. Puntes, Damjana Drobne and Laura Canesi
Nanomaterials 2021, 11(2), 470; https://doi.org/10.3390/nano11020470 - 12 Feb 2021
Cited by 18 | Viewed by 3090
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
Show Figures

Graphical abstract

16 pages, 1792 KiB  
Article
In Vitro Interactions of TiO2 Nanoparticles with Earthworm Coelomocytes: Immunotoxicity Assessment
by Natividad Isabel Navarro Pacheco, Radka Roubalova, Jaroslav Semerad, Alena Grasserova, Oldrich Benada, Olga Kofronova, Tomas Cajthaml, Jiri Dvorak, Martin Bilej and Petra Prochazkova
Nanomaterials 2021, 11(1), 250; https://doi.org/10.3390/nano11010250 - 19 Jan 2021
Cited by 9 | Viewed by 3639
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
Show Figures

Figure 1

19 pages, 3544 KiB  
Article
An OMV-Based Nanovaccine Confers Safety and Protection against Pathogenic Escherichia coli via Both Humoral and Predominantly Th1 Immune Responses in Poultry
by Rujiu Hu, Haojing Liu, Mimi Wang, Jing Li, Hua Lin, Mingyue Liang, Yupeng Gao and Mingming Yang
Nanomaterials 2020, 10(11), 2293; https://doi.org/10.3390/nano10112293 - 20 Nov 2020
Cited by 22 | Viewed by 3500
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
Show Figures

Figure 1

15 pages, 2978 KiB  
Article
Safety Evaluation of TiO2 Nanoparticle-Based Sunscreen UV Filters on the Development and the Immunological State of the Sea Urchin Paracentrotus lividus
by Riccardo Catalano, Jérôme Labille, Daniela Gaglio, Andi Alijagic, Elisabetta Napodano, Danielle Slomberg, Andrea Campos and Annalisa Pinsino
Nanomaterials 2020, 10(11), 2102; https://doi.org/10.3390/nano10112102 - 23 Oct 2020
Cited by 21 | Viewed by 4771
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
Show Figures

Graphical abstract

21 pages, 2926 KiB  
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
by Elmer Swart, Jiri Dvorak, Szabolcs Hernádi, Tim Goodall, Peter Kille, David Spurgeon, Claus Svendsen and Petra Prochazkova
Nanomaterials 2020, 10(7), 1337; https://doi.org/10.3390/nano10071337 - 9 Jul 2020
Cited by 24 | Viewed by 4394
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
Show Figures

Figure 1

Review

Jump to: Editorial, Research

20 pages, 1267 KiB  
Review
The Interactions between Nanoparticles and the Innate Immune System from a Nanotechnologist Perspective
by Lena M. Ernst, Eudald Casals, Paola Italiani, Diana Boraschi and Victor Puntes
Nanomaterials 2021, 11(11), 2991; https://doi.org/10.3390/nano11112991 - 6 Nov 2021
Cited by 39 | Viewed by 9816
Abstract
The immune system contributes to maintaining the body’s functional integrity through its two main functions: recognizing and destroying foreign external agents (invading microorganisms) and identifying and eliminating senescent cells and damaged or abnormal endogenous entities (such as cellular debris or misfolded/degraded proteins). Accordingly, [...] Read more.
The immune system contributes to maintaining the body’s functional integrity through its two main functions: recognizing and destroying foreign external agents (invading microorganisms) and identifying and eliminating senescent cells and damaged or abnormal endogenous entities (such as cellular debris or misfolded/degraded proteins). Accordingly, the immune system can detect molecular and cellular structures with a spatial resolution of a few nm, which allows for detecting molecular patterns expressed in a great variety of pathogens, including viral and bacterial proteins and bacterial nucleic acid sequences. Such patterns are also expressed in abnormal cells. In this context, it is expected that nanostructured materials in the size range of proteins, protein aggregates, and viruses with different molecular coatings can engage in a sophisticated interaction with the immune system. Nanoparticles can be recognized or passed undetected by the immune system. Once detected, they can be tolerated or induce defensive (inflammatory) or anti-inflammatory responses. This paper describes the different modes of interaction between nanoparticles, especially inorganic nanoparticles, and the immune system, especially the innate immune system. This perspective should help to propose a set of selection rules for nanosafety-by-design and medical nanoparticle design. Full article
Show Figures

Figure 1

32 pages, 4325 KiB  
Review
Cross-Species Comparisons of Nanoparticle Interactions with Innate Immune Systems: A Methodological Review
by Benjamin J. Swartzwelter, Craig Mayall, Andi Alijagic, Francesco Barbero, Eleonora Ferrari, Szabolcs Hernadi, Sara Michelini, Natividad Isabel Navarro Pacheco, Alessandra Prinelli, Elmer Swart and Manon Auguste
Nanomaterials 2021, 11(6), 1528; https://doi.org/10.3390/nano11061528 - 9 Jun 2021
Cited by 15 | Viewed by 3812
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
Show Figures

Figure 1

Back to TopTop