Gamma delta T cells and naturally acquired immunity to malaria in neonates
This 3-year project is being carried out in collaboration with the Institute of Immunology, Hannover Medical School, Germany with support from the German Research Foundation. It primarily aims to understand the role of gamma delta (γδ) T cells in the development of naturally acquired immunity to malaria and build capacity in state-of-the-art immunological techniques, next generation sequencing and bioinformatics through the training of postgraduate students.
Gamma delta (γδ) T cells are a set of T cells characterized by their expressed surface γδ T cell receptor (TCR) and show features of both the innate and adaptive arms of the immune system. There is evidence that γδ T cells have protective effector capabilities in various in utero and early childhood infections, including malaria. We recently reported an immediate microbial-driven expansion of fetal-derived human γδ T cells within the first weeks of life that persist until childhood. These microbial-responsive early neonatal γδ T cells can have cytotoxic, but also interleukin 17 production capabilities placing them as important players in the neonate’s immune system.
In this project we aim at strengthening our research collaboration through knowledge transfer of innovative technologies like next-generation sequencing of TCRs and multi-color flow cytometry to study T cells at the NMIMR, Ghana. We will set up a birth cohort of neonates that will be consecutively followed within the first 2-years of life for malaria morbidity and other infectious disease occurrence. Both children born to mothers with or without placental malaria will be included in the study and this will enable us to understand the impact of placental malaria on the postnatal adaptation of neonatal γδ T cell subsets that range from naïve to cytotoxic and Th17-like effector cells. TCR repertoire analysis shall identify disease-associated/protective γδ TCR clones that could be explored in future studies. In addition, the study will assess the interplay between parasite genetic diversity, anti-malarial antibodies and γδ T cells and their potential synergistic effects on the acquisition of natural immunity to malaria that may inform new therapeutic approaches.
In this project our goal is to jointly establish a strong and long-lasting research collaboration that will strengthen research in basic immunology in Ghana and support the training of young Ghanaian researchers for a scientific career. We aim at understanding the impact of neonatal γδ T cells on the natural acquisition of malaria during early childhood.
- To monitoring neonates within the first 2-years of life for malaria infections using a birth cohort.
- To assess the impact of malaria on the postnatal development of γδ T cells and their role in the acquisition of natural malaria immunity.
- To decipher the interplay between parasite genetic diversity, anti-malarial antibody generation and γδ T cell subsets and their potential to orchestrate the acquisition of malaria immunity after birth.
Ethical approval processes are underway, and the study sites have been identified.