P5 - Age-dependent immune responses to Ascaris infections
Supervisor:
Dr. Sebastian Rausch
Lab Address:
Freie Universität Berlin, Institute of Immunology, Centre for Infection Medicine, Robert von Ostertag-Str. 7, D-14163 Berlin
Project description:
Resistance to Ascaris infections depends on T helper 2 (Th2) cells, which produce the cytokines IL-4, -5, and -13. Our work with intestinal nematodes in mice has shown that the number of IFN-γ-competent T helper 1 cells (Th1) increases significantly from juvenile to adult animals, which hinders efficient parasite defence. Furthermore, we were able to show that natural Th2 dominance in the intestinal mucosa of newborn pigs changes to Th1 dominance within a few weeks after birth and that pigs infected with Ascaris develop strong systemic Th1 responses after weaning, while Th2 responses are only moderate.
Based on these findings, the project aims to determine the influence of age-dependent Th1 and IFN-γ competence in Ascaris infections in humans. The doctoral researcher will learn modern immunological techniques of immune cell phenotyping, such as 15-color flow cytometry for intra- and extracellular cell staining, fluorospot assays, and qPCR. Human samples will be obtained in a study in an Ascaris endemic area in Kenya, so the project includes approximately 4 weeks of fieldwork per year in Kenya.
In summary, the project aims to elucidate the influence of age at initial infection and the development of a protective Th2 immune response of the host against roundworms.
References: 1) Kapse et al. 2022, doi: 10.1038/s41385-022-00519-6; 2) Kawabe et al. 2022, doi: 10.3389/fimmu.2022.870542; 3) Schlosser-Brandenburg et al. 2021, doi: 10.3389/fimmu.2021.734153; 4) Oser et al. 2024, doi: 10.3389/fimmu.2024.1396446.