LILRB1 and LILRB2 expression in peripheral blood immune cells at 18 and 24 months of age in infants born from mothers with placental malaria

Dechavanne, C.; Nouatin, O.; Adamou, R.; Edslev, S.; Hansen, A.; Meurisse, F.; Sadissou, I.; Gbaguidi, E.; Milet, J.; Cottrell, G.; Gineau, L.; Sabbagh, A.; Massougbodji, A.; Moutairou, K.; Donadi, E. A.; Carosella, E.; Moreau, P.; Remarque, E.; Theisen, M.; Rouas-Freiss, N.; Garcia, A.; Favier, B.; Courtin, D.

doi:10.1101/2021.10.26.465873

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bioRxiv · 10.1101/2021.10.26.465873

LILRB1 and LILRB2 expression in peripheral blood immune cells at 18 and 24 months of age in infants born from mothers with placental malaria

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Abstract

BackgroundPlacental malaria (PM) is associated with a higher susceptibility of infants to Plasmodium falciparum (Pf) malaria. A hypothesis of immune tolerance has been suggested but no clear explanation has been provided so far. Our goal was to investigate the involvement of inhibitory receptors LILRB1 and LILRB2, known to drive immune evasion upon ligation with pathogen and/or host ligands, in PM-induced immune tolerance. MethodsInfants of mothers with or without PM were enrolled in Allada, southern Benin, and followed-up for 24 months. Antibodies with specificity for five blood stage parasite antigens were quantified by ELISA, and the frequency of immune cell subsets was quantified by flow cytometry. LILRB1 or LILRB2 expression was assessed on cells collected at 18 and 24 months of age. ResultsInfants born to PM-mothers had a higher risk of developing clinical malaria than those born to mothers without PM (IRR=1.53, p=0.040), and such infants displayed a lower frequency of non-classical monocytes (OR=0.74, p=0.01) that overexpressed LILRB2 (OR=1.36, p=0.002). Moreover, infants born to PM-mothers had lower levels of cytophilic IgG and higher levels of IL-10 during active infection. ConclusionModulation of IgG and IL-10 levels could impair monocyte functions (opsonisation/phagocytosis) in infants born to PM-mothers, possibly contributing to their higher susceptibility to malaria. The long-lasting effect of PM on infants monocytes was notable, raising questions about the capacity of ligands such as Rifins or HLA-I molecules to bind to LILRB1 and LILRB2 and to modulate immune responses, and about the reprogramming of neonatal monocytes/macrophages. KEY POINTSInfants of mothers with placental malaria were more susceptible to clinical malaria than those born to mothers without placental malaria and they displayed a lower frequency of non-classical monocytes that overexpressed LILRB2.

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Dechavanne, C., Nouatin, O., Adamou, R., Edslev, S., Hansen, A., Meurisse, F., Sadissou, I., Gbaguidi, E., Milet, J., Cottrell, G., Gineau, L., Sabbagh, A., Massougbodji, A., Moutairou, K., Donadi, E. A., Carosella, E., Moreau, P., Remarque, E., Theisen, M., Rouas-Freiss, N., Garcia, A., Favier, B., Courtin, D.. 2021-10-26. LILRB1 and LILRB2 expression in peripheral blood immune cells at 18 and 24 months of age in infants born from mothers with placental malaria. https://doi.org/10.1101/2021.10.26.465873

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