Age is an intrinsic driver of inflammatory responses to malaria
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Dooley, Nicholas L
Pava, Zuleima
SheelaNair, Arya
Andrew, Dean W
Tipping, Peta
Bourke, Peter
Engwerda, Christian R
Lopez, J Alejandro
Piera, Kim A
William, Timothy
Barber, Bridget E
Grigg, Matthew J
Anstey, Nicholas M
Minigo, Gabriela
et al.
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Abstract
Age is a critical factor in immune responses to infection. In malaria, severe disease risk increases with age in non-immune individuals. Malaria severity is in part driven by inflammation, but mechanisms contributing to age-dependent disease risk are incompletely understood. We assessed inflammatory cytokines during malaria in non-immune children and adults, and innate cell responses in vitro to malaria parasites in naive children and adults. We show during malaria age is associated with increased inflammatory chemokines CCL2, CCL3, CXCL8, CXCL9, along with CRP, and IDO, which associate with symptoms. In naive individuals, classical monocyte and Vδ2+ γδ T cells from adults have higher inflammatory cytokine production, and transcriptional activation following stimulation with parasites. Classical monocyte responses in adults are dominated by CCL2, while in children increased IL10 and enrichment of IL10 signaling pathways is detected. Findings identify age-dependent cellular mechanisms that play crucial roles in driving inflammatory responses in malaria.
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Nature Communications
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16
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© The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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Immunology
Medical virology
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Loughland, JR; Dooley, NL; Pava, Z; SheelaNair, A; Andrew, DW; Tipping, P; Bourke, P; Engwerda, CR; Lopez, JA; Piera, KA; William, T; Barber, BE; Grigg, MJ; Anstey, NM; Minigo, G; et al., Age is an intrinsic driver of inflammatory responses to malaria, Nature Communications, 2025, 16, pp. 8665