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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 3

Previous malaria exposure is reflected in differences in plasma protein profiles.

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Previous malaria exposure is reflected in differences in plasma protein ...
(A) CD107a+ monocytes after stimulation with uninfected (uRBC) or infected red blood cells (iRBC). PBMCs from primary infected (n = 5) and previously exposed individuals (n = 6) from acute and matched 12-month (convalescent) sample time points were stimulated, and degranulation was assessed via surface staining for CD107a. Data are pooled from 2 independent experiments. Primary infected individuals were compared with previously exposed individuals in A and acute samples versus convalescent samples in B. (C–E) PBMCs isolated from healthy donors (n = 11) stimulated with antibody-depleted plasma pools from the acute or convalescent time points for primary infected and previously exposed individuals. A ratio indicating geometric mean fluorescence intensity surface expression changes is shown for classical monocytes (C), intermediate monocytes (D), and nonclassical monocytes (E). Data were pooled from 2 independent experiments. Statistical analysis in A was done using a mixed effects model matched on donor, followed by Šídák’s post hoc test to correct for multiple comparisons. Statistical analysis in B was calculated using 2-tailed matched pair 2-way ANOVA followed by Šídák’s post hoc test for multiple comparisons. Statistical analyses in C–E was done using 2-tailed Student’s t tests; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. See also related Supplemental Figures 2 and 3. Data represent individual donors.

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