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Pneumonia induced trained immunity as a driver of pathogenic inflammation within the lung

Project description

How bacterial pneumonia induces trained immunity

Inflammation plays a key role in respiratory conditions, where previous infections can trigger changes in macrophages. Repeated influenza infections harm the lungs, while bacterial pneumonia increases monocyte production, exacerbating inflammation. Supported by the Marie Skłodowska-Curie Actions programme, the Trained_Lung project will investigate how bacterial pneumonia induces trained immunity, leading to excessive inflammation and lung damage when exposed to other bacteria or environmental pollutants. The project will identify pathogens that train human macrophages, study the secondary inflammatory responses to various bacteria, explore bone marrow myelopoiesis and macrophage function after pneumonia in mice, assess how these changes affect lung function, and examine the impact of trained macrophages on immune responses in iPSC-derived human lung organoids.

Objective

The world health organisation has labeled inflammatory diseases the greatest threat to human health. Inflammation is a major cause of pathogenesis in respiratory conditions such as bronchiectasis, ARDS, and COPD. There is a growing appreciation that our prior pathogen exposure can induce trained immunity in macrophages. Trained_Lung will explore how bacterial pneumonia induces central trained immunity and how this can lead to excessive inflammation and lung damage, in response to other bacteria or environmental pollutants. Recently it has been shown that repeat exposure to influenza can lead to lung damage due to the altered functionality of lung macrophages, leading to excessive inflammation and damage to the structure of the lung. However, it remains unclear if this is the case for bacterial pneumonia and if it can lead to inappropriate inflammatory response upon rechallenge with other bacterial species or environmental pollutants. I propose that bacterial pneumonia will drive enhanced myelopoiesis and enhance circulating monocyte inflammatory responses. Further, these circulating monocytes will replace resident alveolar macrophage populations over time, seeding the lung with these trained monocytes which will become resident alveolar macrophages. Alveolar macrophages are constantly in contact with a range of bacteria, viruses, PAMPs, and pollutants which all have the potential to drive excessive inflammatory responses. Trained_Lung will identify pathogens that can train human macrophages and examine secondary inflammatory responses to a range of bacterial pathogens and environmental pollutants. Further, myelopoietic changes in the bone marrow and functional changes in macrophages post-pneumonia in mice will be explored, and how these changes impact subsequent challenges in terms of lung function and damage. Finally, Trained_Lung will explore how trained macrophages impact immune responses within iPSC-derived human lung organoids, adding a key translational aspect

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

JUSTUS-LIEBIG-UNIVERSITAET GIESSEN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 173 847,36
Address
LUDWIGSTRASSE 23
35390 GIESSEN
Germany

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Region
Hessen Gießen Gießen, Landkreis
Activity type
Higher or Secondary Education Establishments
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Total cost

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