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Role of lymph node phagocytes in the regulation of the IgG-mediated suppression of the immune response to influenza vaccine

English title Role of lymph node phagocytes in the regulation of the IgG-mediated suppression of the immune response to influenza vaccine
Applicant Fernandez Gonzalez Santiago
Number 176124
Funding scheme Project funding
Research institution Istituto di ricerca in biomedicina (IRB) Facoltà di scienze biomedice
Institution of higher education Università della Svizzera italiana - USI
Main discipline Immunology, Immunopathology
Start/End 01.10.2017 - 31.12.2021
Approved amount 700'000.00
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All Disciplines (2)

Discipline
Immunology, Immunopathology
Clinical Immunology and Immunopathology

Keywords (7)

Influenza vaccine; Lymph node macrophages; Immune complex; IgG-mediated immune suppression; Epitope masking; Antigen transport; Intravital two-photon microscopy

Lay Summary (Italian)

Lead
Il presente progetto ha lo scopo di chiarificare i meccanismi con cui agiscono gli anticorpi, che sono fra le più importanti molecole del sistema immunitario.
Lay summary

Sebbene il legame di un anticorpo con il suo specifico bersaglio spesso aumenta la risposta immunitaria contro l’antigene, la presenza di risposte inibitorie è anch’essa un fenomeno comune. Tale processo, definito immunosoppressione anticorpo-mediata (antibody-mediated immune suppression o AMIS), è stato sfruttato con successo in alcune applicazioni cliniche, come la somministrazione di anticorpi specifici contro RhD in gestanti negative, che impedisce loro di diventare immunizzate contro gli eritrociti RhD positivi del feto. Tuttavia, il meccanismo immunologico che porta all’inibizione rimane incompreso. In questo progetto applicheremo la più moderna tecnologia di imaging in vivo per studiare il ruolo che svolgono in tale processo le principali cellule fagocitiche del linfonodo. Ci attendiamo di comprendere il meccanismo molecolare che spinge un anticorpo ad agire come stimolatore piuttosto che come soppressore della risposta immunitaria.

Comprendere come l’inibizione della risposta immunitaria funzioni renderà possibile lo sviluppo di migliori e più efficaci strategie vaccinali e, al contempo, faciliterà la comprensione e lo sviluppo di nuove terapie contro le malattie autoimmuni causate da auto-anticorpi.

Direct link to Lay Summary Last update: 12.10.2017

Responsible applicant and co-applicants

Employees

Publications

Publication
In Vivo Motility Patterns Displayed by Immune Cells Under Inflammatory Conditions
Pizzagalli Diego Ulisse, Pulfer Alain, Thelen Marcus, Krause Rolf, Gonzalez Santiago F. (2022), In Vivo Motility Patterns Displayed by Immune Cells Under Inflammatory Conditions, in Frontiers in Immunology, 12, 5375.
Neutrophil subtypes shape HIV-specific CD8 T-cell responses after vaccinia virus infection
Di Pilato Mauro, Palomino-Segura Miguel, Mejías-Pérez Ernesto, Gómez Carmen E., Rubio-Ponce Andrea, D’Antuono Rocco, Pizzagalli Diego Ulisse, Pérez Patricia, Kfuri-Rubens Raphael, Benguría Alberto, Dopazo Ana, Ballesteros Iván, Sorzano Carlos Oscar S., Hidalgo Andrés, Esteban Mariano, Gonzalez Santiago F. (2021), Neutrophil subtypes shape HIV-specific CD8 T-cell responses after vaccinia virus infection, in npj Vaccines, 6(1), 52-52.
Spatio-temporal profile of innate inflammatory cells and mediators during influenza virus infection
Latino Irene, Gonzalez Santiago F (2021), Spatio-temporal profile of innate inflammatory cells and mediators during influenza virus infection, in Current Opinion in Physiology, 19, 175-186.
Protection against influenza infection requires early recognition by inflammatory dendritic cells through C-type lectin receptor SIGN-R1
Palomino-Segura Miguel, Perez Laurent, Farsakoglu Yagmur, Virgilio Tommaso, Latino Irene, D’Antuono Rocco, Chatziandreou Nikolaos, Pizzagalli Diego U., Wang Guojun, García-Sastre Adolfo, Sallusto Federica, Carroll Michael C., Neyrolles Olivier, Gonzalez Santiago F. (2019), Protection against influenza infection requires early recognition by inflammatory dendritic cells through C-type lectin receptor SIGN-R1, in Nature Microbiology, 4(11), 1930-1940.
Characterization of the Dynamic Behavior of Neutrophils Following Influenza Vaccination
Pizzagalli Diego Ulisse, Latino Irene, Pulfer Alain, Palomino-Segura Miguel, Virgilio Tommaso, Farsakoglu Yagmur, Krause Rolf, Gonzalez Santiago F. (2019), Characterization of the Dynamic Behavior of Neutrophils Following Influenza Vaccination, in Frontiers in Immunology, 10, 2621.
Early production of IL‐17A by γδ T cells in the trachea promotes viral clearance during influenza infection in mice
Palomino‐Segura Miguel, Latino Irene, Farsakoglu Yagmur, Gonzalez Santiago F. (2019), Early production of IL‐17A by γδ T cells in the trachea promotes viral clearance during influenza infection in mice, in European Journal of Immunology, 50(1), 97-109.
A trainable clustering algorithm based on shortest paths from density peaks
Pizzagalli Diego Ulisse, Gonzalez Santiago Fernandez, Krause Rolf (2019), A trainable clustering algorithm based on shortest paths from density peaks, in Science Advances, 5(10), eaax3770-eaax3770.
Engineering polymeric nanocapsules for an efficient drainage and biodistribution in the lymphatic system
Cordeiro Ana Sara, Crecente-Campo José, Bouzo Belén L., González Santiago F., de la Fuente María, Alonso María José (2019), Engineering polymeric nanocapsules for an efficient drainage and biodistribution in the lymphatic system, in Journal of Drug Targeting, 27(5-6), 646-658.
Streptococcus pneumoniaeMethods and Protocols
Palomino-Segura Miguel, Gonzalez Santiago F. (2019), Streptococcus pneumoniaeMethods and Protocols, Springer New York, New York, NY.
Streptococcus pneumoniaeMethods and Protocols
Palomino-Segura Miguel, Gonzalez Santiago F. (2019), Streptococcus pneumoniaeMethods and Protocols, Springer New York, New York, NY.
Influenza Vaccination Induces NK-Cell-Mediated Type-II IFN Response that Regulates Humoral Immunity in an IL-6-Dependent Manner
Farsakoglu Yagmur, Palomino-Segura Miguel, Latino Irene, Zanaga Silvia, Chatziandreou Nikolaos, Pizzagalli Diego Ulisse, Rinaldi Andrea, Bolis Marco, Sallusto Federica, Stein Jens V., Gonzalez Santiago F. (2019), Influenza Vaccination Induces NK-Cell-Mediated Type-II IFN Response that Regulates Humoral Immunity in an IL-6-Dependent Manner, in Cell Reports, 26(9), 2307-2315.e5.
Imaging Cell Interaction in Tracheal Mucosa During Influenza Virus Infection Using Two-photon Intravital Microscopy
Palomino-Segura Miguel, Virgilio Tommaso, Morone Diego, Pizzagalli Diego U., Gonzalez Santiago F. (2018), Imaging Cell Interaction in Tracheal Mucosa During Influenza Virus Infection Using Two-photon Intravital Microscopy, in Journal of Visualized Experiments, (138), e58355.

Datasets

A trainable clustering algorithm based on shortest paths from density peaks

Author Pizzagalli, Diego Ulisse; Gonzalez, Santiago Fernandez; Krause, Rolf
Publication date 30.10.2019
Persistent Identifier (PID) 10.1126/sciadv.aax3770
Repository Sciences advances - supplementary materials
Abstract
Clustering is a technique to analyze empirical data, with a major application for biomedical research. Essentially, clustering finds groups of related points in a dataset. However, results depend on both metrics for point-to-point similarity and rules for point-to-group association. Non-appropriate metrics and rules can lead to artifacts, especially in case of multiple groups with heterogeneous structure. In this work, we propose a clustering algorithm that evaluates the properties of paths between points (rather than point-to-point similarity) and solves a global optimization problem, finding solutions not obtainable by methods relying on local choices. Moreover, our algorithm is trainable. Hence, it can be adapted and adopted for specific datasets and applications by providing examples of valid and invalid paths to train a path classifier. We demonstrate its applicability to identify heterogeneous groups in challenging synthetic datasets, segment highly nonconvex immune cells in confocal microscopy images, and classify arrhythmic heartbeats in electrocardiographic signals.

Collaboration

Group / person Country
Types of collaboration
Adolfo Garcia-Sastre / Mount Sinai Hospital N.Y. United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
Luca Maria Gambardella - USI Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Rolf Krause - Institute of Computational Sciences, USI Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
30th Challenge in Virology Talk given at a conference IDC recognize influenza in the trachea via SIGN-R1 and promote the recruitment of protective NK cells 25.01.2020 Grinderwald , Switzerland Fernandez Gonzalez Santiago;
11th meeting of the European Academy of Dermatology and Venereology (EADV). Talk given at a conference In vivo study of tattoo ink transportation and tattoo-induced inflammation in the draining lymph nodes 21.11.2019 Bellinzona, Switzerland Fernandez Gonzalez Santiago;
Systems Biology of Microbial Infection: Jena Talk given at a conference Describing neutrophil behavior following influenza vaccination from intravital imaging data. 26.09.2019 Jena, Germany Fernandez Gonzalez Santiago;
USI BIOMED PhD Day Poster Study of the IgG-mediated suppression response elicited by different anti-HA antibodies 20.09.2019 Bellinzona, Switzerland Latino Irene;
USI BIOMED PHD Day Talk given at a conference Characterization of the dynamic behavior of neutrophils following influenza vaccination 20.09.2019 Bellinzona, Switzerland Latino Irene;
5th International Symposium on Systems Biology of Microbial Infection (SBMI) Talk given at a conference Describing neutrophil behavior following influenza vaccination from intravital imaging data. 05.09.2019 Jena, Germany Fernandez Gonzalez Santiago;
ProDoc Cell Migration Retreat Poster Study of the IgG-mediated suppression response elicited by different anti-HA antibodies 29.08.2019 Bern, Switzerland Latino Irene;
ECMC Talk given at a conference IDC recognise influenza in the trachea via SIGN-R1 and promote the recruitment of protective NK cells 29.06.2019 Salamanca, Spain Fernandez Gonzalez Santiago;
3rd European Chemokine and Cell Migration Conference Talk given at a conference Inflammatory dendritic cells recognise influenza virus in the trachea via the C-type lectin receptor SIGN-R1 and promote the recruitment of protective NK cells. 23.06.2019 Salamanca, Spain Fernandez Gonzalez Santiago;
41st Congress of the Spanish Society of Immunology Talk given at a conference Intravital characterization of the inflammatory response that follows influenza vaccination in the draining lymph node 30.05.2019 Sevilla, Spain Fernandez Gonzalez Santiago;
41st Congress of Spanish society of Immunology Talk given at a conference Intravital Characterization of the inflammatory response that follows influenza vaccination 30.05.2019 Sevilla, Spain Fernandez Gonzalez Santiago;
IEEE International Symposium on Biomedical Imaging Poster A dataset and a semi-supervised clustering algorithm for segmentation and tracking of immune cells in two-photon microscopy 08.04.2019 Venise, Italy Pulfer Alain;
IRB PhD students retreat Poster Study of the IgG mediated suppression response elicited by different anti HA antibodies 08.04.2019 Weggis, Germany Latino Irene;
ProDoc Cell Migration Retreat Poster The IgG-mediated suppression of different anti-HA antibody is based on their affinity to Fc receptor expressed in dendritic 05.09.2018 Gerzense, Switzerland Latino Irene;
15th Conference on Innate Immunity Talk given at a conference SIGN-R1 recognition of influenza by IDC promotes recruitment and activation of NK cells which leads to the control of the disease in the trachea 19.06.2018 Chania, Greece Fernandez Gonzalez Santiago;
IRB PhD students retreat Poster Study of the IgG mediated suppression response elicited by different anti HA antibodies 02.05.2018 Einsiedeln, Switzerland Latino Irene;


Associated projects

Number Title Start Funding scheme
204636 C-type lectin receptors and their implication in the innate response against respiratory pathogens 01.05.2022 Project funding
189699 IMMUNEMAP: Enabling data-driven immunological research by making two-photon intravital microscopy data FAIR 01.12.2019 Biolink funds
199667 Le molte facce del contagio 01.03.2021 Agora

Abstract

Although the binding of an antigen to a specific immunoglobulin often enhances the antibody response against this antigen, the presence of inhibitory responses is also a common phenomenon. Amongst the latter, the best characterized is the IgG-mediated humoral suppression against large particulate antigens. This process, referred to as antibody-mediated immune suppression (AMIS), has been successfully utilized in clinical applications, such as the administration of specific IgGs to RhD negative mother, which prevents them from becoming immunized against RhD+ fetal erythrocytes. However, the immunological mechanism behind the IgG-mediated immune suppression remains poorly understood. We have developed a passive immunisation protocol that involves the administration of anti-influenza IgG antibodies prior to vaccination, namely H36-7 and FI6, which bind to two different epitopes of the viral HA molecule. Interestingly, these antibodies result in different degrees of suppression of the primary antibody responses to the UV-inactivated influenza vaccine, which was found to be complete in the case of H36-7, but only partial with FI6. Remarkably, the inhibition of the humoral response coincided with a reduction in the initial inflammatory reaction measured in the draining lymph node (LN) at 12 h p.v. and a lower activation of the LN-resident dendritic cells (LNDC).On the basis of our preliminary findings, we propose to study the role that the major phagocytic populations in the LN (LN resident macrophages and LNDC) have on the AMIS, using state-of-the-art in vivo imaging technology, molecular and cellular techniques and the generation of new transgenic mouse models. In addition, we wish to investigate the specific role of the Fc?R and the complement system in immune suppression, and the mechanism through which the AMIS reaction affects the humoural responses to viral epitopes that are not recognized by the administered IgG. We will also characterize the role of RIG-I in the initiation of the type I IFN response following vaccination, and how the formation of immune complexes affects the activation of this pathway.Antibody-mediated immune suppression may represent a powerful tool to modulate adverse immune responses in conditions in which self-antibody-mediated autoimmune diseases present serious health implications. Understanding the mechanism of AMIS may contribute to the discovery of new therapies for such immunological conditions. In addition, understanding the immune response to different type of antigens, can, in turn, inform better vaccine design strategies to develop long-term protective humoral immunity to influenza virus.
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