European Network Linking Informatics and Genomics of Helper T cells in Tissues

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Publication . Kirkby, Margarida Ferreira Pereira Bobela; Graça, Luís; Veldhoen, Marc; Barral, Duarte

Tertiary Lymphoid Structures (TLS) are aggregates of immune cells in non-lymphoid tissue. Located in several organs, they drive immune responses against infections, cancer, and autoimmune diseases. TLS in the lungs, called bronchus-associated lymphoid tissue (BALT) is an ectopic lymphoid structure induced upon infection. In mice, the formation of BALT has been associated with an improved immune response and viral infection control. BALT structurally resembles secondary lymphoid organs (SLO) structures, where the immune response is generated, within a follicle of B cells surrounded by T cells, called the germinal centers (GC). T follicular helper cells (TFH) is one of the main T cell subsets found in BALT. They have the capacity to help B cells generate high-affinity antibodies. The ability to use and manipulate BALT to enhance immune responses presents possibilities for more effective vaccination strategies. In order to manipulate BALT in the lungs, our aim is to understand how to elicit an effective immune response from this structure. To test this hypothesis, we used three models of infection, the virus Influenza X31 (Type 1), the helminth Nippostrongyllus brasiliensis (Type 2), and the fungi Aspergillus fumigatus (Type 3). Next, we examined BALT formation across various infection types. We hypothesize that BALT formation in the lungs involves the recruitment of TFH cells and that the lung's CD4 helper cell compartment exhibits corresponding polarization to the infection type. To address this research question, we developed a new infection protocol and used spectral cytometry to study the formation of BALT. After infecting with Influenza X31 and Aspergillus fumigatus, we observed TFH and GC B cells, which together could be used as a proxy for BALT formation. We visually confirmed these findings with histopathological analysis using H&E staining and immunohistochemistry (IHC). We observed structures in the Aspergillus-infected lungs that are presumptive of BALT formation. In the case of Nippostrongylus infection, mainly in the mediastinal lymph nodes, which are known for draining the lung, we also observed an increase in the cell types associated with BALT presence, supporting the idea that TLS can form in the lungs following infection. Further experiments are necessary to strengthen our findings. In addition, we aim to explore the impact of BALT on the lung microbiome following these three types of infections. These next steps will help us better understand the role of BALT in lung infections and may provide new insights for treating respiratory diseases.

2024-11-21Dissertação de mestrado

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Entidade financiadora

European Commission

Programa de financiamento

H2020

Número da atribuição

955321