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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 6

BAFF-R levels are affected by the plasma microenvironment and soluble BAFF.

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BAFF-R levels are affected by the plasma microenvironment and soluble BA...
(A) Schematic illustration of the in vitro experimental setup for plasma stimulations of PBMCs. Plasma was pooled from primary infected (n = 8) or previously exposed (n = 8) donors while PBMCs were isolated from healthy blood donors (n = 11). (B) Geometric mean fluorescence intensity (geoMFI) of BAFF-R levels on gated B cells 24 hours after culture with indicate plasma pools. (C) Comparison of the BAFF-R geoMFI ratio for acute over 12-month plasma for primary infected and previously exposed donors. Statical analysis in B was done using a paired 2-tailed Student’s t tests and, in C, an unpaired 2-tailed Student’s t test. ***P < 0.001, ****P < 0.0001. (D) Schematic illustration of the experimental setup for recombinant BAFF stimulations of purified B cells. (E) BAFF-R geoMFI ratios between nonstimulated and BAFF, anti-Ig+CpGC, or anti-Ig+CpGC+BAFF stimulated sorted B cells after 2 days (n = 11) (E) or 4 days (n = 4) (F) of culture. Statistical analyzes in E and F were done using repeated-measures 1-way ANOVA followed by Šídák’s post hoc test with *P < 0.05, **P < 0.01. See also related Supplemental Figure 7. Data represent individual donors.

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