Different routes, same pathways: molecular mechanisms under silver ion and nanoparticle exposures in the soil sentinel Eisenia fetida

Use of nanotechnology products is increasing; with silver (Ag) nanoparticles particularly widely used. A key uncertainty surrounding the risk assessment of AgNPs is whether their effects are driven through the same mechanism of action that underlies the toxic effects of Ag ions. We present the first full transcriptome study of the effects of Ag ions and NPs in an ecotoxicological model soil invertebrate, the earthworm Eisenia fetida. Gene expression analyses indicated similar mechanisms for both silver forms with toxicity being exerted through pathways related to ribosome function, sugar and protein metabolism, molecular stress, disruption of energy production and histones. The main difference seen between Ag ions and NPs was associated with potential toxicokinetic effects related to cellular internalisation and communication, with pathways related to endocytosis and cilia being significantly enriched. These results point to a common final toxicodynamic response, but initial internalisation driven by different exposure routes and toxicokinetic mechanisms

Identification of a Newly Conserved SLA-II Epitope in a Structural Protein of Swine Influenza Virus

Despite the role of pigs as a source of new Influenza A Virus viruses (IAV) potentially capable of initiating human pandemics, immune responses to swine influenza virus (SwIV) in pigs are not fully understood. Several SwIV epitopes presented by swine MHC (SLA) class I have been identified using different approaches either in outbred pigs or in Babraham large white inbred pigs, which are 85% identical by genome wide SNP analysis. On the other hand, some class II SLA epitopes were recently described in outbred pigs. In this work, Babraham large white inbred pigs were selected to identify SLA II epitopes from SwIV H1N1. PBMCs were screened for recognition of overlapping peptides covering the NP and M1 proteins from heterologous IAV H1N1 in IFNγ ELISPOT. A novel SLA class II restricted epitope was identified in NP from swine H1N1. This conserved novel epitope could be the base for further vaccine approaches against H1N1 in pigs.info:eu-repo/semantics/publishedVersio

Uptake routes and toxicokinetics of silver nanoparticles and silver ions in the earthworm Lumbricus rubellus

Current bioavailability models, such as the free ion activity model and biotic ligand model, explicitly consider that metal exposure will be mainly to the dissolved metal in ionic form. With the rise of nanotechnology products and the increasing release of metal-based nanoparticles (NPs) to the environment, such models may increasingly be applied to support risk assessment. It is not immediately clear, however, whether the assumption of metal ion exposure will be relevant for NPs. Using an established approach of oral gluing, a toxicokinetics study was conducted to investigate the routes of silver nanoparticles (AgNPs) and Ag+ ion uptake in the soil-dwelling earthworm Lumbricus rubellus. The results indicated that a significant part of the Ag uptake in the earthworms is through oral/gut uptake for both Ag+ ions and NPs. Thus, sealing the mouth reduced Ag uptake by between 40% and 75%. An X-ray analysis of the internal distribution of Ag in transverse sections confirmed the presence of increased Ag concentrations in exposed earthworm tissues. For the AgNPs but not the Ag+ ions, high concentrations were associated with the gut wall, liver-like chloragogenous tissue, and nephridia, which suggest a pathway for AgNP uptake, detoxification, and excretion via these organs. Overall, the results indicate that Ag in the ionic and NP forms is assimilated and internally distributed in earthworms and that this uptake occurs predominantly via the gut epithelium and less so via the body wall. The importance of oral exposure questions the application of current metal bioavailability models, which implicitly consider that the dominant route of exposure is via the soil solution, for bioavailability assessment and modeling of metal-based NPs

Unique metabolites protect earthworms against plant polyphenols

All higher plants produce polyphenols, for defence against above-ground herbivory. These polyphenols also influence the soil micro- and macro-fauna that break down plant leaf litter. Polyphenols therefore indirectly affect the fluxes of soil nutrients and, ultimately, carbon turnover and ecosystem functioning in soils. It is unknown how earthworms, the major component of animal biomass in many soils, cope with high-polyphenol diets. Here, we show that earthworms possess a class of unique surface-active metabolites in their gut, which we term ‘drilodefensins’. These compounds counteract the inhibitory effects of polyphenols on earthworm gut enzymes, and high-polyphenol diets increase drilodefensin concentrations in both laboratory and field populations. This shows that drilodefensins protect earthworms from the harmful effects of ingested polyphenols. We have identified the key mechanism for adaptation to a dietary challenge in an animal group that has a major role in organic matter recycling in soils worldwide

Therapeutic administration of broadly neutralizing FI6 antibody reveals lack of interaction between human IgG1 and pig Fc receptors

Influenza virus infection is a significant global health threat. Because of the lack of cross-protective universal vaccines, short time window during which antivirals are effective and drug resistance, new therapeutic anti-influenza strategies are required. Broadly, cross-protective antibodies that target conserved sites in the hemagglutinin (HA) stem region have been proposed as therapeutic agents. FI6 is the first proven such monoclonal antibody to bind to H1–H16 and is protective in mice and ferrets. Multiple studies have shown that Fc-dependent mechanisms are essential for FI6 in vivo efficacy. Here, we show that therapeutic administration of FI6 either intravenously or by aerosol to pigs did not reduce viral load in nasal swabs or broncho-alveolar lavage, but aerosol delivery of FI6 reduced gross pathology significantly. We demonstrate that pig Fc receptors do not bind human IgG1 and that FI6 did not mediate antibody-dependent cytotoxicity (ADCC) with pig PBMC, confirming that ADCC is an important mechanism of protection by anti-stem antibodies in vivo. Enhanced respiratory disease, which has been associated with pigs with cross-reactive non-neutralizing anti-HA antibodies, did not occur after FI6 administration. Our results also show that in vitro neutralizing antibody responses are not a robust correlate of protection for the control of influenza infection and pathology in a natural host model

Spatial, temporal and molecular dynamics of swine influenza virus-specific CD8 tissue resident memory T cells

For the first time we have defined naïve, central memory, effector memory and differentiated effector porcine CD8 T cells and analyzed their distribution in lymphoid and respiratory tissues after influenza infection or immunization, using peptide-MHC tetramers of three influenza nucleoprotein (NP) epitopes. The hierarchy of response to the three epitopes changes during the response in different tissues. Most NP-specific CD8 T cells in broncho-alveolar lavage (BAL) and lung are tissue resident memory cells (TRM) that express CD69 and downregulate CD45RA and CCR7. NP-specific cells isolated from BAL express genes characteristic of TRM, but gene expression differs at 7, 21 and 63 days post infection. In all tissues the frequency of NP-specific CD8 cells declines over 63 days almost to background levels but is best maintained in BAL. The kinetic of influenza specific memory CD8 T cell in this natural host species differs from that in small animal models

Comparison of heterosubtypic protection in ferrets and pigs induced by a single-cycle influenza vaccine

Influenza is a major health threat, and a broadly protective influenza vaccine would be a significant advance. Signal Minus FLU (S-FLU) is a candidate broadly protective influenza vaccine that is limited to a single cycle of replication, which induces a strong cross-reactive T cell response but a minimal Ab response to hemagglutinin after intranasal or aerosol administration. We tested whether an H3N2 S-FLU can protect pigs and ferrets from heterosubtypic H1N1 influenza challenge. Aerosol administration of S-FLU to pigs induced lung tissue-resident memory T cells and reduced lung pathology but not the viral load. In contrast, in ferrets, S-FLU reduced viral replication and aerosol transmission. Our data show that S-FLU has different protective efficacy in pigs and ferrets, and that in the absence of Ab, lung T cell immunity can reduce disease severity without reducing challenge viral replication

Vaccine-mediated protection of pigs against infection with pandemic H1N1 2009 swine influenza A virus requires a close antigenic match between the vaccine antigen and challenge virus

Swineandnbsp;influenza A virusandnbsp;(SwIV) infection has considerable economic and animal welfare consequences and, because of the zoonotic potential, can also have public health implications. The 2009 pandemicandnbsp;H1N1andnbsp;andlsquo;swine-originandrsquo; infection is now endemic in both pigs and humans. In Europe, avian-like H1avN1, human-like H1huN2, human-like swineandnbsp;H3N2andnbsp;and, since 2009, pandemic H1N1 (pH1N1) lineage viruses andandnbsp;reassortants, constitute the dominant subtypes. In this study, we used a swine pH1N1 challenge virus to investigate the efficacy ofandnbsp;whole inactivated virus vaccinesandnbsp;homologous or heterologous to the challenge virus as well as a commercial vaccine. We found that vaccine-mediated protection was most effective when vaccine antigen and challenge virus were homologous and correlated with the specific production ofandnbsp;neutralising antibodiesandnbsp;and a cellular response to the challenge virus. We conclude that a conventional whole inactivated SwIV vaccine must be antigenically matched to the challenge strain to be an effective control measure.</p