Antifungal T-cell responses of neonates, infants, and children
Immunology
Final Report Abstract
In order to understand the role of T cell-mediated immunity in early life infections, particularly in children under the age of five, our project focused on the age-specific differentiation and defence capabilities of human T cells. Our first aim was to analyse antigen-specific T cell activation. Age-dependent T cell proliferation was observed, revealing differences in responses to different pathogens, especially fungi. Bioorthogonal non-canonical amino acid tagging (BONCAT) allowed us to follow protein synthesis in neonatal, infant and adult T cells, revealing age-specific differences. Our second aim was to study neonatal and infant Th17 cells, which are crucial for protection against infection. We identified age-specific patterns in IL-17 production, with preterm infants showing an increased frequency of IL-17 producers. Furthermore, Bifidobacterium longum ssp. infantis (B. infantis) induced Treg-like cells, challenging previous assumptions that B. infantis is merely a placeholder in the neonatal gut. Our investigation into the age-dependent use of STAT molecules provided initial insights, and research into B. infantis and Th cell responses highlighted the intricate interplay between T cell responses and regulatory mechanisms. In summary, our research has provided valuable insights into age-specific T cell dynamics, revealed potential predispositions at birth and highlighted the complexity of the mechanisms used in the immune system in neonates and infants.
Publications
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Immune-checkpoint blockade of CTLA-4 (CD152) in antigen-specific human T-cell responses differs profoundly between neonates, children, and adults. OncoImmunology, 10(1).
Arra, Aditya; Pech, Maximilian; Fu, Hang; Lingel, Holger; Braun, Franziska; Beyer, Christian; Spiliopoulou, Myra; Bröker, Barbara M.; Lampe, Karen; Arens, Christoph; Vogel, Katrin; Pierau, Mandy & Brunner-Weinzierl, Monika C.
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Age-related Differences in Immune Reactions to SARS-CoV-2 Spike and Nucleocapsid Antigens. In vivo 37:70-78
Morhart P., Kehl S., Schuh W., Hermes K., Meltendorf S., Neubert A., Schneider M., Brunner-Weinzierl M., Schneider H. & Lingel H.
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Bifidobacteria shape antimicrobial T-helper cell responses during infancy and adulthood. Nature Communications, 14(1).
Vogel, Katrin; Arra, Aditya; Lingel, Holger; Bretschneider, Dirk; Prätsch, Florian; Schanze, Denny; Zenker, Martin; Balk, Silke; Bruder, Dunja; Geffers, Robert; Hachenberg, Thomas; Arens, Christoph & Brunner-Weinzierl, Monika C.
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PD-1/PD-L1 Control of Antigen-Specifically Activated CD4 T-Cells of Neonates. International Journal of Molecular Sciences, 24(6), 5662.
Majer, Christiane; Lingel, Holger; Arra, Aditya; Heuft, Hans-Gert; Bretschneider, Dirk; Balk, Silke; Vogel, Katrin & Brunner-Weinzierl, Monika C.
