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

• Published in: Nature communications Vol. 15; no. 1; p. 2021
• Main Authors: Tebben, Kieran, Yirampo, Salif, Coulibaly, Drissa, Koné, Abdoulaye K., Laurens, Matthew B., Stucke, Emily M., Dembélé, Ahmadou, Tolo, Youssouf, Traoré, Karim, Niangaly, Amadou, Berry, Andrea A., Kouriba, Bourema, Plowe, Christopher V., Doumbo, Ogobara K., Lyke, Kirsten E., Takala-Harrison, Shannon, Thera, Mahamadou A., Travassos, Mark A., Serre, David
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06-03-2024; Nature Publishing Group; Nature Portfolio
• Subjects: 38/39; 45/91; 631/1647/514; 631/250/255/1629; 631/326/417/2546; Age; Children; Correlation; Extravasation; Gametocytes; Gene expression; Gene sequencing; Humanities and Social Sciences; Immune system; Infections; Leukocytes (neutrophilic); Lymphocytes; Lymphocytes T; Malaria; multidisciplinary; Neutrophils; Parasitemia; Parasites; Plasmodium falciparum; Science; Science (multidisciplinary); Variation; Vector-borne diseases
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-46416-3

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.
Here the authors use dual RNA sequencing to characterize host and parasite gene expression from 136 Malian children with symptomatic
Plasmodium falciparum
infection. They find that parasitemia levels correlate with neutrophil and T cell levels and that the child’s age correlates with innate immune gene expression as well as gametocyte levels.