Project

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Intravital imaging of polymicrobial respiratory diseases (IMPORED)

Applicant Fernandez Gonzalez Santiago
Number 148183
Funding scheme Ambizione
Research institution Istituto di ricerca in biomedicina (IRB) Facoltà di scienze biomedice
Institution of higher education Università della Svizzera italiana - USI
Main discipline Medical Microbiology
Start/End 01.01.2014 - 31.12.2016
Approved amount 618'050.00
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All Disciplines (2)

Discipline
Medical Microbiology
Immunology, Immunopathology

Keywords (5)

intravital 2-photon microscopy; Streptococcus pneumoniae; Microarray analysis; microbiome; Influenza virus

Lay Summary (French)

Lead
L'objectif principal de IMPORED est d'étudier l'interaction entre deux des agents pathogènes respiratoires les plus importants pour l’humain, le virus de la grippe et Streptococcus pneumoniae et de caractériser la réponse immunitaire de l'hôte face à cette co-infection. Utilisant des outils moléculaires, nous allons essayer de décrire un modèle permettant de prédire quand une infection par le virus de la grippe peut évoluer vers une infection secondaire pneumocale dangereuse.
Lay summary
Les infections respiratoires sont l'une des principales causes de morbidité et de mortalité dans le monde. Parmi les principaux agents pathogènes des voies respiratoires, le virus de la grippe et Streptococcus pneumoniae (le pneumocoque) ont un impact sur la santé et sont responsables de milliards d'argent public perdus chaque année. D’une façon générale, les études scientifiques ont mis l'accent sur ??les infections dues à un seul agent pathogène. Cependant, il a été démontré que, dans certains cas, la co-infection avec une combinaison particulière d'agents pathogènes entraîne un symptôme clinique plus sévère par rapport à une infection due à un seul pathogène. Cependant, les mécanismes par lesquels le virus de la grippe peut faciliter les infections secondaires dues au pneumocoque restent flous. Ce projet  concerne l'étude des interactions hôte-pathogène lors de co-infections impliquant le virus de la grippe et S. pneumoniae, en utilisant des techniques moléculaires (analyse de microbiome, l'analyse de microarray) et des méthodes de microscopie de pointe (microscopie intravitale à 2 photons) chez un modèle murin. Nous allons utiliser les co-infections bien connues du virus de la grippe et du Streptococcus pneumoniae pour analyser leurs interactions avec les bactéries commensales et étudier la réponse de l'hôte. Comme second objectif, nous allons examiner in vivo les effets que les mécanismes moléculaires, identifiés dans l'objectif précédent, ont sur le développement d'une infection secondaire à pneumocoques.
Direct link to Lay Summary Last update: 02.10.2013

Lay Summary (English)

Lead
The main goal of IMPORED is to study the interaction between two of the most important respiratory pathogens in humans, influenza virus and Streptococcus pneumoniae and to characterize the immune response in the host against a co-infection with both pathogens. Using molecular tools we will try to describe a model to predict when an infection with influenza virus will evolve to a dangerous pneumocal secondary infection.
Lay summary
Respiratory infections are one the leading causes of morbidity and mortality worldwide. Amongst the major respiratory pathogens, influenza virus and Streptococcus pneumoniae (the pneumococcus), have a health impact that is also responsible for billions in public money lost every year. Typically, scientific studies have focused on infections with single pathogens. However, it has been demonstrated that, in some cases, co-infection with a particular combination of pathogens results in a more severe clinical outcome compared with infection with either pathogen alone. Nevertheless, the mechanisms by which influenza infection may facilitate pneumococcal secondary infections remain unclear. This proposal regards the investigation of the host-pathogen interactions upon co-infection with influenza virus and S. pneumoniae, using state-of-the-art molecular techniques (microbiome analysis, microarray analysis) and intravital microscopy methods (2-photon microscopy) in the mouse model. We will use the well-studied association between influenza virus and Streptococcus pneumoniae infections to inform our investigation of their interaction with the other commensal bacterium and the host response. In the second aim we will examine in vivo the effects that the molecular mechanisms identified in the previous aim have in the establishment of a pneumococcal secondary infection.
Direct link to Lay Summary Last update: 02.10.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Dynamic intravital imaging of cell-cell interactions in the lymph node
Stein Jens V., F. Gonzalez Santiago (2017), Dynamic intravital imaging of cell-cell interactions in the lymph node, in Journal of Allergy and Clinical Immunology, 139(1), 12-20.
Macrophage Death following Influenza Vaccination Initiates the Inflammatory Response that Promotes Dendritic Cell Function in the Draining Lymph Node
Chatziandreou Nikolaos, Farsakoglu Yagmur, Palomino-Segura Miguel, D’Antuono Rocco, Pizzagalli Diego Ulisse, Sallusto Federica, Lukacs-Kornek Veronika, Uguccioni Mariagrazia, Corti Davide, Turley Shannon J., Lanzavecchia Antonio, Carroll Michael C., Gonzalez Santiago F. (2017), Macrophage Death following Influenza Vaccination Initiates the Inflammatory Response that Promotes Dendritic Cell Function in the Draining Lymph Node, in Cell Reports, 18(10), 2427-2440.

Collaboration

Group / person Country
Types of collaboration
Prof. Michael Carroll United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Jens Stein Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Thorsten Mempel United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
Dr. Adolfo Garcia-Sastre / Mount Sinai School of Medicine United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Maria Jose Alonso / University of Santiago de Compostela Spain (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Adriano Aguzzi Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Mariano Esteban / Centro Nacional de Biotechnologia Spain (Europe)
- Exchange of personnel
Dr. Cornelia Halin / ETH Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Andrea Cerutti United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
EADV meeting Bellinzona 2016 Talk given at a conference Macrophages associated secretion of IL-1 alpha promotes dendritic cell function and induces B cell response after influenza vaccination 01.12.2016 Bellinzona, Switzerland Fernandez Gonzalez Santiago;
International Congress of Immunology Talk given at a conference Characterization of the inflammatory response in the upper respiratory tract following influenza infection 22.08.2016 Melbourne, Australia Palomino Segura Miguel;
13th International Conference on Innate Immunity Talk given at a conference Macrophages as initiators of the immune response in the lymph node 27.06.2016 Rhodes, Greece Fernandez Gonzalez Santiago;
Invited lecture at the master in BioSciences from Homeostasis to Disease (ENS Lyon) Individual talk Trafficking of antigen in the lymphatic system following vaccination 26.05.2016 Lyon, France Fernandez Gonzalez Santiago;
Invited lecture at the Institute of Neuropathology Individual talk Role of the early inflammatory response that follows vaccination in the adaptive immunity 04.05.2016 Zurich, Switzerland Fernandez Gonzalez Santiago;
4th ProDoc Cell Migration Workshop Talk given at a conference Study of the immune response in the upper respiratory tract to secondary pneumococcal challenge after influenza infection 17.11.2015 Bern, Switzerland Palomino Segura Miguel;
Special Invited Speaker, International center for infectiology Research (CIRI) INSERM. Universite Lyon 1 Individual talk Lymph node macrophages as first line mediators of the immune response 28.09.2015 Lyon, France Fernandez Gonzalez Santiago;
ABS Animal Science Day 2015 Individual talk Intravital microscopy in mice 11.09.2015 Bern, Switzerland Fernandez Gonzalez Santiago;
Toll 2015 Meeting Targeting Innate Immunity Poster Lymph node macrophages as first line mediators of the immune response 01.09.2015 Marbella, Spain Fernandez Gonzalez Santiago;
3rd ProDoc CellMigration Retreat Poster Intravital Imaging Of Polymicrobial Respiratory Diseases 11.02.2015 Weggis, Switzerland Palomino Segura Miguel;


Self-organised

Title Date Place
Imaging the Immune Sytem 23.10.2014 San Raffaele Institute (Milano), Italy

Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Vaccination as preventive medicine Italian-speaking Switzerland 2016

Associated projects

Number Title Start Funding scheme
145038 Acquisition of a 2-Photon microscope for intravital analysis 01.12.2012 R'EQUIP

Abstract

Respiratory infections are one the leading causes of morbidity and mortality worldwide. Amongst the major respiratory pathogens, influenza virus and Streptococcus pneumoniae (the pneumococcus), have a health impact that is also responsible for thousands of millions of public money lost every year. Typically, scientific studies have focused on infections with single pathogens. However, it has been demonstrated that, in some cases, co-infection with a particular combination of pathogens results in a more severe clinical outcome compared with infection with either pathogen alone. Nevertheless, the mechanisms by which influenza co-infection may facilitate pneumococcal secondary infections remain unclear.This proposal regards the investigation of the host-pathogen interactions upon co-infection with influenza virus and S. pneumoniae, using state-of-the-art molecular techniques (microbiome analysis, microarray analysis) and intravital microscopy methods (2-photon microscopy) in the mouse model. To this end, two aims are proposed. The first aim of the project is to characterise the molecular mechanisms that lead to the transition from normal microbiota to an infected state in the upper respiratory tract, taking into account the host-pathogen interactions that lead to infection. We will use the well-studied association between influenza virus and Streptococcus pneumoniae infections to inform our investigation of their interaction with the upper respiratory tract microbiome and the host response. We will develop a predictive model of how the transcriptome and microbiome signature of the host may be affected in response to a challenge (for instance an influenza infection) so that we can analyse the possibility that this perturbation could lead to a secondary, more dangerous, disease such as pneumococcal infection.In the second aim we will examine in vivo the effects that the molecular mechanisms identified in the previous aim have in the establishment of a pneumococcal secondary infection. We will develop an intravital 2-photon microscopy model of the mouse trachea and different fluorescent strains of influenza and pneumococcus will be produced to visualize their interaction with the host tissue. This technique will allow us the monitor the dynamics of the co-infection in real time.
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