Hyaluronic acid-decorated liposomes as innovative targeted delivery system for lung fibrotic cells

Collagen Tissue Disease-associated Interstitial Lung Fibrosis (CTD-ILDs) and Bronchiolitis Obliterans Syndrome (BOS) represent severe lung fibrogenic disorders, characterized by fibro-proliferation with uncontrolled extracellular matrix deposition. Hyaluronic acid (HA) plays a key role in fibrosis with its specific receptor, CD44, overexpressed by CTD-ILD and BOS cells. The aim is to use HA-liposomes to develop an inhalatory treatment for these diseases. Liposomes with HA of two molecular weights were prepared and characterized. Targeting efficiency was assessed toward CTD-ILD and BOS cells by flow cytometry and confocal microscopy and immune modulation by RT-PCR and ELISA techniques. HA-liposomes were internalized by CTD-ILD and BOS cells expressing CD44, and this effect increased with higher HA MW. In THP-1 cells, HA-liposomes decreased pro-inflammatory cytokines IL-1\u3b2, IL-12, and anti-fibrotic VEGF transcripts but increased TGF-\u3b2 mRNA. However, upon analyzing TGF-\u3b2 release from healthy donors-derived monocytes, we found liposomes did not alter the release of active pro-fibrotic cytokine. All liposomes induced mild activation of neutrophils regardless of the presence of HA. HA liposomes could be also applied for lung fibrotic diseases, being endowed with low pro-inflammatory activity, and results confirmed that higher MW HA are associated to an increased targeting efficiency for CD44 expressing LFs-derived from BOS and CTD-ILD patients

Human cytomegalovirus-specific CD4(+) and CD8(+) T-cell response determination: comparison of short-term (24h) assays vs long-term (7-day) infected dendritic cell assay in the immunocompetent and the immunocompromised host.

Human cytomegalovirus (HCMV)-specific CD4(+) and CD8(+) T-cells were measured in the immunocompetent host as well as in 13 solid-organ transplant recipients (SOTR), and 12 young hematopoietic stem cell transplant recipients (HSCTR) by using a long-term (7-day) assay based on PBMC stimulation by HCMV-infected dendritic cells (iDC), and two short-term (24h) assays, one for CD4(+) stimulation by infected cell lysate (iCL), and the other for CD8(+) stimulation by a pool of 34 epitopic peptides (pep-pool). In the immunocompetent, the number of T-cells activated by either iCL or the pep-pool was significantly reduced with respect to iDC. In both SOTR and HSCTR, the number of T-cells activated by iDC was comparable to that activated by iCL or the pep-pool. A significant correlation between iDC-activated T-cells and T-cells activated by either iCL or the pep-pool was observed. In conclusion, whenever a rapid result is needed, short-term assays may efficiently replace the iDC assay

Monitoring of human cytomegalovirus-specific CD4 and CD8 T-cell immunity in patients receiving solid organ transplantation

Absolute and human cytomegalovirus (HCMV)- specific CD4+ and CD8+ T-cell counts were monitored in 38 solid organ (20 heart, 9 lung and 9 kidney) transplant recipients during the first year after transplantation by a novel assay based on T-cell stimulation with HCMV-infected autologous dendritic cells. According to the pattern of T-cell restoration occurring either within the first month after transplantation or later, patients were classified as either early (n = 21) or late responders (n = 17). HCMV-specific CD4+ and CD8+ T-cell counts were consistently lower in late compared to early responders from baseline through 6 months after transplantation. In addition, in late responders, while HCMV infection preceded immune restoration, HCMV-specific CD4+ restoration was significantly delayed with respect to CD8+ T-cell restoration. The number of HCMV-specific CD4+ and CD8+ T-cells detected prior to transplantation significantly correlated with time to T-cell immunity restoration, in that higher HCMV-specific T-cell counts predicted earlier immune restoration. Clinically, the great majority of early responders (18/21, 85.7%) underwent self-resolving HCMV infections (p = 0.004), whereas the great majority of late responders (13/17, 76.5%) were affected by HCMV infections requiring antiviral treatment (p = <0.0001). Simultaneous monitoring of HCMV infection and HCMV-specific T-cell immunity predicts T-cell-mediated control of HCMV infection

Welfare barriers and levers for improvement in organic and low-input outdoor pig and poultry production systems

International audienceThe PPILOW project aims to co-construct innovations to improve Poultry and Pig Welfare in Low-input outdoor and Organic farming systems through a multi-actor approach. Its first step was to sum up animal welfare challenges observed in these systems and levers of improvement, from a review of literature data and research projects. Data were completed with information from key informants of the supply chains of poultry meat, eggs and pork in Italy, France, the United Kingdom and Finland. The interviews indicated that the main issues in poultry were: feeding, biosecurity, lack of range use and range management, feather pecking, weather, regulation, flock size or density, predation, bone fractures, lack of robustness, parasitism, pododermatitis, arthrosis, nervousness, water quality, catching and time spent by farmers. The main issues in pig were: feeding, tail biting, mortality, weather, predation, lack of robustness, lack of range use, castration, animal aggressiveness and competition, water quality, range management, human welfare, biosecurity issues, flock size or density, parasitism, insolation burns, joint abnormalities, parturition in freedom and pollution. This information has implemented a participatory approach for proposing welfare-improvement levers. Some issues and potential solutions were included in PPILOW experiments (phytotherapy against parasitism, involvement of animal personality in range use, rearing of entire pig males, genetic selection for reduced piglet mortality, improved farrowing huts for sows and piglets reared on range, avoiding feather pecking in laying hens with intact beaks, avoiding the killing of day-old male chicks etc.), and solution costs evaluated. The results will provide a combination of practical solutions for welfare improvement in Europe. The PPILOW project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement N°816172

Welfare barriers and levers for improvement in organic and low-input outdoor pig and poultry production systems

International audienceThe PPILOW project aims to co-construct innovations to improve Poultry and Pig Welfare in Low-input outdoor and Organic farming systems through a multi-actor approach. Its first step was to sum up animal welfare challenges observed in these systems and levers of improvement, from a review of literature data and research projects. Data were completed with information from key informants of the supply chains of poultry meat, eggs and pork in Italy, France, the United Kingdom and Finland. The interviews indicated that the main issues in poultry were: feeding, biosecurity, lack of range use and range management, feather pecking, weather, regulation, flock size or density, predation, bone fractures, lack of robustness, parasitism, pododermatitis, arthrosis, nervousness, water quality, catching and time spent by farmers. The main issues in pig were: feeding, tail biting, mortality, weather, predation, lack of robustness, lack of range use, castration, animal aggressiveness and competition, water quality, range management, human welfare, biosecurity issues, flock size or density, parasitism, insolation burns, joint abnormalities, parturition in freedom and pollution. This information has implemented a participatory approach for proposing welfare-improvement levers. Some issues and potential solutions were included in PPILOW experiments (phytotherapy against parasitism, involvement of animal personality in range use, rearing of entire pig males, genetic selection for reduced piglet mortality, improved farrowing huts for sows and piglets reared on range, avoiding feather pecking in laying hens with intact beaks, avoiding the killing of day-old male chicks etc.), and solution costs evaluated. The results will provide a combination of practical solutions for welfare improvement in Europe. The PPILOW project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement N°816172

The PPILOW project: Innovations improving welfare in low input and organic pig and poultry farms

International audienceThe PPILOW project aims to co-construct innovations to improve Poultry and Pig Welfare in Low-input outdoor and Organic farming systems through a multi-actor approach. PPILOW implements a participatory approach for proposing and studying welfare-improvement levers. It will provide a combination of practical solutions that can be applied at a pan-European level with specific adjustments depending on citizen’s expectations and the target market. The multi-actor approach consists in involving end-users including farmers, breeding companies, feed producers, consumer associations, retailers, advisers, processors, and scientists in National Practitioner Groups (NPG) in six participating countries. PPILOW partners facilitate the groups by connecting NPG at European level, transferring scientific information, interacting with partners engaged in animal experiments, and co-creating innovations rising from NPG-specific demands. They co-build with PPILOW partners welfare self-assessment tools (development of the PIGLOW app for pigs and refinement of the EBENE® app for poultry), and innovative breeding, feeding, and rearing strategies and techniques to improve the welfare of animals. They co-design protocols, test innovations on farm, and disseminate the results. In turn, they receive insights on methods and scientific results, and inputs from other NPG reinforcing the value of the expected outcomes. Approaches focus on avoiding physical damage and the elimination of layer male chicks, on reducing boar taint of intact male pigs, promoting positive behaviours, animal health, and robustness through field studies with pigs and poultry. Multicriteria analyses of the most effective levers of welfare improvement will be performed to evaluate their economic, social, and environmental impacts based on the ‘One Welfare’ concept; economic and business models will also be developed. To ensure the rapid uptake of the project results by end-users, the close involvement of PPILOW’s NPG throughout the EU will ensure disseminationactivities and the facilitation of change. The PPILOW project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement N°816172. www.ppilow.eu

The PPILOW project: Innovations improving welfare in low input and organic pig and poultry farms

International audienceThe PPILOW project aims to co-construct innovations to improve Poultry and Pig Welfare in Low-input outdoor and Organic farming systems through a multi-actor approach. PPILOW implements a participatory approach for proposing and studying welfare-improvement levers. It will provide a combination of practical solutions that can be applied at a pan-European level with specific adjustments depending on citizen’s expectations and the target market. The multi-actor approach consists in involving end-users including farmers, breeding companies, feed producers, consumer associations, retailers, advisers, processors, and scientists in National Practitioner Groups (NPG) in six participating countries. PPILOW partners facilitate the groups by connecting NPG at European level, transferring scientific information, interacting with partners engaged in animal experiments, and co-creating innovations rising from NPG-specific demands. They co-build with PPILOW partners welfare self-assessment tools (development of the PIGLOW app for pigs and refinement of the EBENE® app for poultry), and innovative breeding, feeding, and rearing strategies and techniques to improve the welfare of animals. They co-design protocols, test innovations on farm, and disseminate the results. In turn, they receive insights on methods and scientific results, and inputs from other NPG reinforcing the value of the expected outcomes. Approaches focus on avoiding physical damage and the elimination of layer male chicks, on reducing boar taint of intact male pigs, promoting positive behaviours, animal health, and robustness through field studies with pigs and poultry. Multicriteria analyses of the most effective levers of welfare improvement will be performed to evaluate their economic, social, and environmental impacts based on the ‘One Welfare’ concept; economic and business models will also be developed. To ensure the rapid uptake of the project results by end-users, the close involvement of PPILOW’s NPG throughout the EU will ensure disseminationactivities and the facilitation of change. The PPILOW project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement N°816172. www.ppilow.eu