Gene expression analyses reveal differences in children’s response to malaria according to their age

Kieran Tebben, Salif Yirampo, Drissa Coulibaly, Abdoulaye K. Koné, Matthew B. Laurens, Emily M. Stucke, Ahmadou Dembélé, Youssouf Tolo, Karim Traoré, Amadou Niangaly, Andrea A. Berry, Bourema Kouriba, Christopher V. Plowe, Ogobara K. Doumbo, Kirsten E. Lyke, Shannon Takala-Harrison, Mahamadou A. Thera, Mark A. Travassos and David Serre ()
Additional contact information
Kieran Tebben: University of Maryland School of Medicine
Salif Yirampo: University of Sciences, Techniques and Technologies
Drissa Coulibaly: University of Sciences, Techniques and Technologies
Abdoulaye K. Koné: University of Sciences, Techniques and Technologies
Matthew B. Laurens: University of Maryland School of Medicine
Emily M. Stucke: University of Maryland School of Medicine
Ahmadou Dembélé: University of Sciences, Techniques and Technologies
Youssouf Tolo: University of Sciences, Techniques and Technologies
Karim Traoré: University of Sciences, Techniques and Technologies
Amadou Niangaly: University of Sciences, Techniques and Technologies
Andrea A. Berry: University of Maryland School of Medicine
Bourema Kouriba: University of Sciences, Techniques and Technologies
Christopher V. Plowe: University of Maryland School of Medicine
Ogobara K. Doumbo: University of Sciences, Techniques and Technologies
Kirsten E. Lyke: University of Maryland School of Medicine
Shannon Takala-Harrison: University of Maryland School of Medicine
Mahamadou A. Thera: University of Sciences, Techniques and Technologies
Mark A. Travassos: University of Maryland School of Medicine
David Serre: University of Maryland School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract In Bandiagara, Mali, children experience on average two clinical malaria episodes per year. However, even in the same transmission area, the number of uncomplicated symptomatic infections, and their parasitemia, can vary dramatically among children. We simultaneously characterize host and parasite gene expression profiles from 136 Malian children with symptomatic falciparum malaria and examine differences in the relative proportion of immune cells and parasite stages, as well as in gene expression, associated with infection and or patient characteristics. Parasitemia explains much of the variation in host and parasite gene expression, and infections with higher parasitemia display proportionally more neutrophils and fewer T cells, suggesting parasitemia-dependent neutrophil recruitment and/or T cell extravasation to secondary lymphoid organs. The child’s age also strongly correlates with variations in gene expression: Plasmodium falciparum genes associated with age suggest that older children carry more male gametocytes, while variations in host gene expression indicate a stronger innate response in younger children and stronger adaptive response in older children. These analyses highlight the variability in host responses and parasite regulation during P. falciparum symptomatic infections and emphasize the importance of considering the children’s age when studying and treating malaria infections.

Date: 2024
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DOI: 10.1038/s41467-024-46416-3

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