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Dissecting the molecular pathogenesis of Legionella spp. in human lung models

Aging populations and the increasing use of immune modulatory medical treatments have given rise to a growing incidence of opportunistic infections. Legionella species are Gram-negative environmental bacteria, which after accident... ver más

31/07/2021

THE QUEEN'S UNIVER...

213K€

Presupuesto del proyecto: 213K€

Líder del proyecto

THE QUEENS UNIVERSITY OF BELFAST No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2021-07-31

MSCA-IF-2018: Individual Fellowships

I+D

Cerrada hace 6 años

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No hay información privada compartida para este proyecto. Habla con el coordinador.

1 Participantes

THE QUEEN'S UNIVERSITY OF BE...

212.93K€ | Lider

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Duración del proyecto: 27 meses Fecha Inicio: 2019-04-10
Fecha Fin: 2021-07-31

Líder del proyecto

THE QUEENS UNIVERSITY OF BELFAST No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 213K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Aging populations and the increasing use of immune modulatory medical treatments have given rise to a growing incidence of opportunistic infections. Legionella species are Gram-negative environmental bacteria, which after accidental inhalation can cause respiratory infections with symptoms reaching from a mild flu to a severe pneumonia, called Legionnaires’ disease. Disease progression, i.e. clearance or exacerbation of infection, is determined by the immune status of the host and acute pneumonia usually associated with immune suppression and/or underlying pulmonary conditions, but the molecular mechanisms enhancing susceptibility are poorly understood. The infection biology of Legionella has been studied mostly in cellular infection models and mice, which do not develop human-like disease. As patients typically present only at late stages of infection, it is unclear to which extent findings from these models reflect the early processes which occur in the human lung during infection and how these drive the clinical outcomes. Similarly, these models fail to explain, why L. pneumophila serogroup 1 strains are the predominant cause of more than 90% of Legionnaires’ disease cases. In this project I, the applicant Dr. Flavia Viana, will tackle these knowledge gaps by establishing and using human precision cut lung tissue slices (hPCLS) and excorporeal perfused whole human lungs (Ex vivo lung perfusion (EVLP)) as infection models for Legionella. I will determine if and how virulence of different Legionella isolates in these models correlates with their relevance in the clinical practice, analyse the transcriptional responses of all cell types in the infected human tissue using single cell transcriptomics and employ histology, state-of-the-art confocal and light sheet live microscopy, to visualise infection dynamics and host responses, providing unprecedented insight into the molecular events leading to the development of Legionnaires’ disease.

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