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Previous malaria exposure attenuates monocyte-driven inflammation and correlates with modulation of the B cell response
Maximilian Julius Lautenbach, Pengjun Xi, Linn Kleberg, Alan-Dine Courey-Ghaouzi, Maia Serene Gower, Carolina Sousa Silva, Felicia Chammas, Anna Färnert, Christopher Sundling
Maximilian Julius Lautenbach, Pengjun Xi, Linn Kleberg, Alan-Dine Courey-Ghaouzi, Maia Serene Gower, Carolina Sousa Silva, Felicia Chammas, Anna Färnert, Christopher Sundling
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Research Article Immunology Infectious disease

Previous malaria exposure attenuates monocyte-driven inflammation and correlates with modulation of the B cell response

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Abstract

Clinical immunity to malaria develops after repeated malaria episodes. In this process, the inflammatory response is modulated to respond less vigorously upon reinfection. Monocytes are a major source of proinflammatory mediators during blood-stage infection and are known to adapt to repeated pathogen exposure. Here, we investigated the effect of previous malaria exposure on monocytes during blood-stage malaria by comparing the response in previously exposed and primary infected individuals. We observed reduced levels of several proinflammatory chemokines in previously exposed individuals, linked to changes in monocytes. Similarly, BAFF levels were lower in these individuals and associated with modulation of monocyte and dendritic cells. This affected the BAFF/BAFF-R axis, crucial for B cell responses, correlating with increasing parasite-specific antibody levels. Collectively, we present insights into how previous malaria exposure shapes monocyte responses during acute malaria and how these, in turn, correlate with modulation of the B cell compartment and humoral immune response.

Authors

Maximilian Julius Lautenbach, Pengjun Xi, Linn Kleberg, Alan-Dine Courey-Ghaouzi, Maia Serene Gower, Carolina Sousa Silva, Felicia Chammas, Anna Färnert, Christopher Sundling

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Figure 4

Plasma protein differences associated with malaria in individuals with primary infection versus previous exposure.

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Plasma protein differences associated with malaria in individuals with p...
Differential protein abundance between primary infected (n = 10) and previously exposed individuals (n = 21), based on a linear mixed-effects model accounting for interdonor variation, with FDR correction (Benjamini-Hochberg, 0.05) applied throughout. (A) Volcano plot comparing NPX values between primary infected and previously exposed donors (controlling for donor and time) and highlighting the top 10 differentially abundant proteins (DAPs) ranked by adjusted P value and NPX difference. (B) Protein abundance of the top 10 significant proteins (all have adjusted P ≤ 0.05) across acute and convalescent (M12) states. (C) Heatmap of ΔNPX (Acute–M12) for all significant DAPs, annotated with NPX differences and –log10(adjusted P values). Parameter estimate indicates the estimated difference in protein abundance.

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