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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 1

Transcriptomics profiles of monocytes during acute malaria.

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Transcriptomics profiles of monocytes during acute malaria.
(A) UMAP rep...
(A) UMAP representation of 73,121 CD45+ immune cells during and after acute malaria based on weighted nearest neighbor integrated targeted transcriptomic and epitope single-cell profiling, previously published by Lautenbach et al. (19). (B) Digital isolation of monocyte subsets of all 3 sampling time points; during acute P. falciparum malaria (Acute), approximately 10 days after treatment (D10) and at a healthy state 1 year after disease (M12). (C) Density plots for monocytes during acute malaria (only acute samples) for typical monocyte surface markers CD14 and CD16. (D) Hallmark gene expression sets enriched in monocytes of acute compared with the M12 healthy state (nAcute = 4, nM12 = 4). Red indicates higher in acute and blue higher in M12. FDR corrected P values were calculated using camera. See also related Supplemental Figure 1.

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