Gillian Mbambo

United States

Host immunotranscriptomics during malaria infection and malaria-schistosomiasis co-infection in a Malian pediatric cohort

Gillian Mbambo1, Joana C. Silva1, Kirsten E Lyke2, Abdoulaye Dabo3, Charles Arama3, Issa Diarra3, Ogobara K Doumbo3

1. Institute of Genome Sciences, University of Maryland, School of Medicine, Baltimore, Maryland
2. Center for Vaccine Development and Global Health, University of Maryland, School of Medicine, Baltimore, Maryland
3. Malaria Research and Training Center, International Centers for Excellence in Research (NIH), University of Science Techniques and Technologies of Bamako, Bamako, Mali

Abstract

Background

Malaria caused by Plasmodium falciparum remains a significant public health challenge, particularly in children from highly endemic regions. Immune responses during acute infection and post-clearance are not fully understood, especially in the presence of co-infections such as Schistosoma haematobium. This study aimed to characterize immune cell populations and gene expression in children aged 4-8 during acute P. falciparum infection and several months following parasite clearance.

Methods

Single-cell RNA-sequencing was performed on peripheral blood mononuclear cells (PBMCs) from 20 children in Mali to identify distinct immune cell subsets and assess transcriptional changes. We analyzed major immune cell populations, including T cells, B cells, natural killer (NK) cells, and myeloid cells. Differential expression analysis was conducted to determine the impact of P. falciparum infection and S. haematobium co-infection on immune cell composition and gene expression.

Results

Our analysis revealed significant gene expression changes associated with P. falciparum infection, whereas S. haematobium co-infection did not significantly alter gene expression profiles. Notably, we identified a cytotoxic CD4 T cell population enriched in Th1 cells. Differential expression analysis demonstrated increased expression of lymphocyte activation gene 3 (LAG3), basic leucine zipper ATF-like transcription factor (BATF), interferon, and interleukin 18 (IL18) receptor genes across distinct CD4 T cell subsets during acute malaria. Additionally, we observed upregulation of NR4A transcription factors in P. falciparum-negative, malaria-exposed children, suggesting their role in T cell dysfunction and potential implications for sub-optimal immunity.

Conclusions

These findings provide new insights into the immune response to P. falciparum in children and highlight key transcriptional regulators such as BATF and NR4A family members. The dynamic gene expression patterns suggest a complex immune response influenced by antigenic exposure. Further research is needed to elucidate the mechanisms shaping immune responses to malaria and co-infections, with potential implications for therapeutic strategies.