Complement Decay-Accelerating Factor is a modulator of influenza A virus lung immunopathology

Clearance of viral infections, such as SARS-CoV-2 and influenza A virus (IAV), must be fine-tuned to eliminate the pathogen without causing immunopathology. As such, an aggressive initial innate immune response favors the host in contrast to a detrimental prolonged inflammation. The complement pathway bridges innate and adaptive immune system and contributes to the response by directly clearing pathogens or infected cells, as well as recruiting proinflammatory immune cells and regulating inflammation. However, the impact of modulating complement activation in viral infections is still unclear. In this work, we targeted the complement decay-accelerating factor (DAF/CD55), a surface protein that protects cells from non-specific complement attack, and analyzed its role in IAV infections. We found that DAF modulates IAV infection in vivo, via an interplay with the antigenic viral proteins hemagglutinin (HA) and neuraminidase (NA), in a strain specific manner. Our results reveal that, contrary to what could be expected, DAF potentiates complement activation, increasing the recruitment of neutrophils, monocytes and T cells. We also show that viral NA acts on the heavily sialylated DAF and propose that the NA-dependent DAF removal of sialic acids exacerbates complement activation, leading to lung immunopathology. Remarkably, this mechanism has no impact on viral loads, but rather on the host resilience to infection, and may have direct implications in zoonotic influenza transmissions.This work was funded by Instituto Gulbenkian de Ciência (IGC), Fundac¸ão Calouste Gulbenkian (FCG) and Fundação para a Ciência e a Tecnologia (FCT) (PTDC/IMI-MIC/1142/2012). NBS was funded by Graduate Programme Science for Development (PGCD) and FCG. ZEVS was funded by FCT (SFRH/BD/52179/2013). CG was funded by FCT (POCI-01-0145-FEDER-29780, PTDC/MEDQUI/29780/2017). CAR was funded by FCT (POCI-01-0145-FEDER-007274, UID/BIM/04293). MJA is funded by FCT (2020.02373.CEECIND). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

A comparison of Helicobacter pylori and non-Helicobacter pylori Helicobacter spp. Binding to Canine Gastric Mucosa with Defined Gastric Glycophenotype

Background: The gastric mucosa of dogs is often colonized by non-Helicobacter pylori helicobacters (NHPH), while H. pylori is the predominant gastric Helicobacter species in humans. The colonization of the human gastric mucosa by H. pylori is highly dependent on the recognition of host glycan receptors. Our goal was to define the canine gastric mucosa glycophenotype and to evaluate the capacity of different gastric Helicobacter species to adhere to the canine gastric mucosa. Materials and Methods: The glycosylation profile in body and antral compartments of the canine gastric mucosa, with focus on the expression of histo-blood group antigens was evaluated. The in vitro binding capacity of FITC-labeled H. pylori and NHPH to the canine gastric mucosa was assessed in cases representative of the canine glycosylation pattern. Results: The canine gastric mucosa lacks expression of type 1 Lewis antigens and presents a broad expression of type 2 structures and A antigen, both in the surface and glandular epithelium. Regarding the canine antral mucosa, H. heilmannii s.s. presented the highest adhesion score whereas in the body region the SabA-positive H. pylori strain was the strain that adhered more. Conclusions: The canine gastric mucosa showed a glycosylation profile different from the human gastric mucosa suggesting that alternative glycan receptors may be involved in Helicobacter spp. binding. Helicobacter pylori and NHPH strains differ in their ability to adhere to canine gastric mucosa. Among the NHPH, H. heilmannii s.s. presented the highest adhesion capacity in agreement with its reported colonization of the canine stomach.We kindly thank Prof. Thomas Boren from the Department of Medical Biochemistry and Biophysics, Umea University, Sweden for providing the 17875/Leb and 17875babA1A2H. pylori strains. The authors thank Dr. Fernando Rodrigues, Dr. Ana Laura Saraiva, and Cristina Bacelar who kindly provided technical support. I. Amorim (SFRH/BD/76237/2011) and A. Magalhães (SFRH/BPD/75871/2011) acknowledge FCT for financial support. This study was partially funded by the Portuguese Foundation for Science and Technology (PTDC/CTM-BPC/121149/2010; PTDC/CVT/117610/2010; PTDC/BBB-EBI/0786/2012). The Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education and is partially supported by FCT

Conceptual Framework for Managing Uncertainty in a Collaborative Agri-Food Supply Chain Context

[EN] Agri-food supply chains are subjected to many sources of uncertainty. If these uncertainties are not managed properly, they can have a negative impact on the agri-food supply chain (AFSC) performance, its customers, and the environment. In this sense, collaboration is proposed as a possible solution to reduce it. For that, a conceptual framework (CF) for managing uncertainty in a collaborative context is proposed. In this context, this paper seeks to answer the following research questions: What are the existing uncertainty sources in the AFSCs? Can collaboration be used to reduce the uncertainty of AFSCs? Which elements can integrate a CF for managing uncertainty in a collaborative AFSC? The CF proposal is applied to the weather source of uncertainty in order to show its applicability.The first author acknowledges the partial support of the Program of Formation of University Professors of the Spanish Ministry of Education, Culture, and Sport (FPU15/03595). The other authors acknowledge the partial support of the Project 691249, RUC-APS: Enhancing and implementing Knowledge based ICT solutions within high Risk and Uncertain Conditions for Agriculture Production Systems, funded by the EU under its funding scheme H2020-MSCA-RISE-2015.Esteso-Álvarez, A.; Alemany Díaz, MDM.; Ortiz Bas, Á. (2017). Conceptual Framework for Managing Uncertainty in a Collaborative Agri-Food Supply Chain Context. IFIP Advances in Information and Communication Technology. 506:715-724. https://doi.org/10.1007/978-3-319-65151-4_64S715724506Taylor, D.H., Fearne, A.: Towards a framework for improvement in the management of demand in agri-food supply chains. Supply Chain Manag. Int. J. 11, 379–384 (2006)Matopoulos, A., Vlachopoulou, M., Manthou, V., Manos, B.: A conceptual framework for supply chain collaboration: empirical evidence from the agri-food industry. Supply Chain Manag. Int. 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Up-regulation of Toll-like receptors 2, 3 and 4 in allergic rhinitis

BACKGROUND: Toll-like receptors enable the host to recognize a large number of pathogen-associated molecular patterns such as bacterial lipopolysaccharide, viral RNA, CpG-containing DNA and flagellin. Toll-like receptors have also been shown to play a pivotal role in both innate and adaptive immune responses. The role of Toll-like receptors as a primary part of our microbe defense system has been shown in several studies, but their possible function as mediators in allergy and asthma remains to be established. The present study was designed to examine the expression of Toll-like receptors 2, 3 and 4 in the nasal mucosa of patients with intermittent allergic rhinitis, focusing on changes induced by exposure to pollen. METHODS: 27 healthy controls and 42 patients with seasonal allergic rhinitis volunteered for the study. Nasal biopsies were obtained before and during pollen season as well as before and after allergen challenge. The seasonal material was used for mRNA quantification of Toll-like receptors 2, 3 and 4 with real-time polymerase chain reaction, whereas specimens achieved in conjunction with allergen challenge were used for immunohistochemical localization and quantification of corresponding proteins. RESULTS: mRNA and protein representing Toll-like receptors 2, 3 and 4 could be demonstrated in all specimens. An increase in protein expression for all three receptors could be seen following allergen challenge, whereas a significant increase of mRNA only could be obtained for Toll-like receptor 3 during pollen season. CONCLUSION: The up-regulation of Toll-like receptors 2, 3 and 4 in the nasal mucosa of patients with symptomatic allergic rhinitis supports the idea of a role for Toll-like receptors in allergic airway inflammation

Tracking Antigen-Specific T-Cells during Clinical Tolerance Induction in Humans

Allergen immunotherapy presents an opportunity to define mechanisms of induction of clinical tolerance in humans. Significant progress has been made in our understanding of changes in T cell responses during immunotherapy, but existing work has largely been based on functional T cell assays. HLA-peptide-tetrameric complexes allow the tracking of antigen-specific T-cell populations based on the presence of specific T-cell receptors and when combined with functional assays allow a closer assessment of the potential roles of T-cell anergy and clonotype evolution. We sought to develop tools to facilitate tracking of antigen-specific T-cell populations during wasp-venom immunotherapy in people with wasp-venom allergy. We first defined dominant immunogenic regions within Ves v 5, a constituent of wasp venom that is known to represent a target antigen for T-cells. We next identified HLA-DRB1*1501 restricted epitopes and used HLA class II tetrameric complexes alongside cytokine responses to Ves v 5 to track T-cell responses during immunotherapy. In contrast to previous reports, we show that there was a significant initial induction of IL-4 producing antigen-specific T-cells within the first 3–5 weeks of immunotherapy which was followed by reduction of circulating effector antigen-specific T-cells despite escalation of wasp-venom dosage. However, there was sustained induction of IL-10-producing and FOXP3 positive antigen-specific T cells. We observed that these IL-10 producing cells could share a common precursor with IL-4-producing T cells specific for the same epitope. Clinical tolerance induction in humans is associated with dynamic changes in frequencies of antigen-specific T-cells, with a marked loss of IL-4-producing T-cells and the acquisition of IL-10-producing and FOXP3-positive antigen-specific CD4+ T-cells that can derive from a common shared precursor to pre-treatment effector T-cells. The development of new approaches to track antigen specific T-cell responses during immunotherapy can provide novel insights into mechanisms of tolerance induction in humans and identify new potential treatment targets

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT