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Dissecting the human microbiota-macrophage-innate lymphoid cell crosstalk in the lung

Periodic Reporting for period 1 - MICRO-MACRO-ILC (Dissecting the human microbiota-macrophage-innate lymphoid cell crosstalk in the lung)

Reporting period: 2016-12-01 to 2018-11-30

Inflammatory lung diseases, such as chronic obstructive airways disease and asthma, lead to significant morbidity and mortality, but today no cure exists for these important diseases. Chronic inflammation is caused by an excessive immune response, which leads to tissue damage and impaired lung function. Recently, changes in our “normal” bacterial flora (the so-called microbiota) have been associated with chronic inflammatory diseases in humans. However, it is poorly understood if and how these microbiota changes cause human disease. The main aim of this project is to understand how the interaction between the human immune system and the microbiota maintains normal lung function and how this interaction is disturbed in lung inflammation. For this purpose, we are using an innovative model to study the human immune system and its interaction with the microbiota in vivo.
We have established a new experimental model, which allows us to investigate how the microbiota regulates human immune function in the lung. The use of our innovative in vivo model makes the results more relevant to humans, given that important differences exist between mice and humans in terms of the immune system, inflammatory responses, and the microbiota. At the beginning of the project, the MSC Fellow/researcher obtained in-depth training in all the experimental techniques required for the project. Specifically, the Fellow learned how to generate and work with the new model developed by the supervisor in order to study human lung immunity in vivo. In addition, the Fellow gained a lot of knowledge about the microbiota field and the latest developments in the area of immunology. During the rest of the 10 month reporting period, significant progress has been made in obtaining the objectives of the proposed work packages. A further improved version of the model was validated and used to demonstrate that important human immune cell types can be study in vivo in our new model. The experiments to examine how the microbiota regulates human immune function have been initiated. Finally, a model to study lung inflammation has been set up.
All research findings obtained so far in this project have been disseminated by presenting them at research seminars and joint meetings with collaborators. The final results of the project will be published in high-impact scientific journals with the MSC Fellow/researcher as a co-author.
We expect that the findings from this project will be beneficial to the general public in Europe. First, the project has implications for the understanding of inflammatory lung diseases that are very common in Europe and cause a significant health care and economic burden. Moreover, our new approach has the potential to discover better ways to treat important human lung diseases. Second, the project will promote Europe’s competitiveness in this research field by studying the human immune system in vivo and its role in human lung disease. Therefore, the timeliness of the project and the host laboratory’s unique expertise may significantly contribute to research excellence in Europe.
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