Dr Collins M. Morang’a @collinsmisita is a Postdoctoral Fellow at the West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana. He received his Bachelor of Science degree in Biochemistry from Egerton University, Kenya and his Master of Science Degree in Cell and Molecular Biology from Maseno University, Kenya. He completed his PhD at the University of Ghana, where his research focused on using flow cytometry and single-cell RNA sequencing to understand the immunological and transcriptomic differences between clinical and subclinical malaria infections. Currently his postdoctoral research work aims to use single cell RNA-Seq and ATAC-Seq to understand epigenetic and cellular immunological differences in children with severe malaria using longitudinal studies. In addition, Collins is a member of the Africa Bioinformatics Network (ABN) and Human Cell Atlas (HCA) Africa Network, where he contributes to planning of computational workshops/Activities for early career scientists in Africa.
Comparative analysis of cellular immune responses in children with subclinical and clinical malaria in Ghana
Authors: Collins M. Morang’a1, Riley S. Drake2,3,4,5, Vincent N. Miao2,3,4,5, Nancy K. Nyakoe1, Dominic S.Y. Amuzu1, Vincent Appiah1, Yaw Aniweh1, Yaw Bediako1, Saikou Y. Bah6, Alex K. Shalek2,3,4,5, Thomas D. Otto6 & Lucas Amenga–Etego1, Gordon A. Awandare1,*
1West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Legon, Accra, Ghana
2Program in Health Sciences & Technology, Harvard Medical School & Massachusetts Institute of Technology, Boston, MA 02115, USA
3Institute for Medical Engineering & Science (IMES), Department of Chemistry, and Koch Institute for Integrative Cancer Research, MIT, Cambridge, Massachusetts, 02139, USA
4Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA
5Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
6School of Infection & Immunity, MVLS, University of Glasgow, Glasgow, UK
Malaria causes significant morbidity and mortality worldwide, disproportionately impacting children in sub-Saharan Africa. Disease phenotypes associated with malarial infection can vary widely, subclinical to severe and life-threatening. Vaccine development efforts have been hindered by an incomplete understanding of the factors that influence host immune responses to infection and their impact on disease outcomes. We applied single-cell RNA-sequencing (scRNA-Seq) to compare the immunological phenotypes of peripheral blood mononuclear cells (PBMCs) isolated from children with subclinical or clinical malarial infections in an area of high malaria transmission in northern Ghana. Overall, clinical paediatric malaria infections were characterized by a higher fractional abundance of monocytes, and an upregulation of innate immune responses such as type I and type II interferons and tumor necrosis factor alpha (TNF-a) signalling via nuclear factor kappa B (NFkB); however, we found substantial intra- and inter individual variation in the transcriptional signatures of circulating immune cells across our cohort. Furthermore, in the clinical malaria group we identified putative interactions between antigen presenting cells and proliferating CD4 T cells, effector memory C4 T cells, and naïve CD8 T cells, driven by MHC-I and MHC-II signalling pathways that were not observed in subclinical group. Together, these findings suggest that transcriptional differences between immune cell subsets may determine disease phenotypes. The findings provide new insights that will guide the development of improved malaria vaccines for individuals residing in endemic areas.