Project

Discipline

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

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

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

Active participation

Self-organised

Communication	Title	Media	Place	Year

Number	Title	Start	Funding scheme

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.