UPECBCG

Cellular and molecular mechanisms of bladder immune responses to uropathogens and therapeutics

Coordinatore	INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)    more  Organization address address: 101 Rue de Tolbiac city: PARIS postcode: 75654 contact info Titolo: Ms. Nome: Laurie Cognome: Louis-Joseph Email: send email Telefono: +33 1 45 17 29 79 Fax: +33 1 45 17 29 11
Nazionalità Coordinatore	France [FR]
Totale costo	100˙000 €
EC contributo	100˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2012-CIG
Funding Scheme	MC-CIG
Anno di inizio	2013
Periodo (anno-mese-giorno)	2013-02-01   -   2017-01-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)  Organization address address: 101 Rue de Tolbiac city: PARIS postcode: 75654 contact info Titolo: Ms. Nome: Laurie Cognome: Louis-Joseph Email: send email Telefono: +33 1 45 17 29 79 Fax: +33 1 45 17 29 11	FR (PARIS)	coordinator	100˙000.00

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 Obiettivo del progetto (Objective)

'The bladder is a unique mucosal barrier devoid of colonizing microbiota and organized lymphoid structures. This research project will examine bladder immunobiology, specifically as it relates to urinary tract infection (UTI) and bladder cancer. Notably, UTI is second only to respiratory infection in prevalence, and bladder cancer is the fifth leading cause of cancer. While commonalities between UTI and bladder cancer may not be immediately apparent, the most effective treatment for transitional cell carcinoma is intravesical instillation of BCG, or the direct introduction of bacteria into the bladder lumen. We will investigate bladder immune responses following uropathogenic E. coli (UPEC) or BCG instillation, with the aim to identify how dendritic cells (DCs) and T cells behave following bacterial interactions with what is a unique mucosal surface in the body. Specifically, we will test the hypotheses that (i) bladder-resident macrophages acquire UPEC antigen in the bladder and sequester it from DCs, limiting antigen presentation, while lymph node-resident DCs capture disseminated BCG and efficiently present it; and (ii) DCs that do capture UPEC antigen lack the ability to cross-present antigen whereas BCG-antigen loaded DCs have a greater capacity to activate CD8 T cells. These hypotheses are based on animal model and clinical observations and will help establish a scientific foundation for exploring strategies to enhance UPEC antigen-specific responses, taking lessons from BCG’s capacity to induce cross-priming. The goal of these studies is to understand the differential outcomes in adaptive immune responses to BCG or UPEC thereby defining strategies to enhance clearance of UPEC and improve the efficacy of BCG-mediated tumor immunity. My dual training as a microbiologist and immunologist will ensure that attention is given to both the bacterium and the host in defining the differential regulation governing the respective disease processes.'