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

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 5

BAFF-R levels on B cells are reduced during acute malaria and highly negatively correlated with circulating BAFF levels.

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BAFF-R levels on B cells are reduced during acute malaria and highly neg...
(A) Representative FACS plots of BAFF-R expression on total live lymphocytes at acute P. falciparum malaria or after 12 months (left and middle panel) and for CD19+ CD20+ B cells at all time points (right panel). (B) Longitudinal assessment of BAFF-R expression on CD19+CD20+ B cells at and after acute P. falciparum malaria. The points denote the mean with error bars showing the SEM. The gray lines indicate data from individual donors. Healthy individuals (Ctrl) as a reference with dotted line of their mean (n = 14) (C). Comparison of CD19+CD20+BAFF-R+ B cells during acute malaria for primary infected (purple, n = 15) and previously exposed individuals (orange, n = 28). Mean of control group as dotted line as in B. (D) Relative protein abundance NPX of BAFF (TNFSF13B) in primary infected and previously exposed individuals over the sampling time points, assessed using linear mixed-effects models accounting for repeated measures. *P < 0.05, ****P < 0.0001. (E) Association between plasma BAFF (TNFSF13B) levels and CD19+CD20+ B cell surface BAFF-R (MFI) levels during acute infection using a multiple linear regression model with BAFF and prior exposure status as predictors. The correlation coefficient (R2) was corrected for multiple testing (BAFF, exposure, BAFF × exposure). The line represents the fitted linear regression model with 95% CI. See also related Supplemental Figure 6. Data represent individual donors.