Osteopontin and malaria: no direct effect on parasite growth, but correlation with P. falciparum-specific B cells and BAFF in a malaria endemic area

Susanne E Mortazavi,Muyideen Kolapo Tijani,Fred Kironde,Allan Lugaajju,Mark Kaddumukasa,Kristina E M Persson

doi:10.1186/s12866-021-02368-y

Abstract

BackgroundThe dysregulation of B cell activation is prevalent during naturally acquired immunity against malaria. Osteopontin (OPN), a protein produced by various cells including B cells, is a phosphorylated glycoprotein that participates in immune regulation and has been suggested to be involved in the immune response against malaria. Here we studied the longitudinal concentrations of OPN in infants and their mothers living in Uganda, and how OPN concentrations correlated with B cell subsets specific for P. falciparum and B cell activating factor (BAFF). We also investigated the direct effect of OPN on P. falciparum in vitro.ResultsThe OPN concentration was higher in the infants compared to the mothers, and OPN concentration in infants decreased from birth until 9 months. OPN concentration in infants during 9 months were independent of OPN concentrations in corresponding mothers. OPN concentrations in infants were inversely correlated with total atypical memory B cells (MBCs) as well as P. falciparum-specific atypical MBCs. There was a positive correlation between OPN and BAFF concentrations in both mothers and infants. When OPN was added to P. falciparum cultured in vitro, parasitemia was unaffected regardless of OPN concentration.ConclusionsThe concentrations of OPN in infants were higher and independent of the OPN concentrations in corresponding mothers. In vitro, OPN does not have a direct effect on P. falciparum growth. Our correlation analysis results suggest that OPN could have a role in the B cell immune response and acquisition of natural immunity against malaria.

Highlights

The dysregulation of B cell activation is prevalent during naturally acquired immunity against malaria
Characteristics of participants Blood samples from 80 mother-infant pairs were included in the analysis of OPN concentration
The OPN concentrations and variations in OPN concentration in infants did not change when linear mixed models were used to adjust for OPN concentrations in corresponding mothers, supporting the conclusion that the source of OPN in cord blood is either the fetus itself or that it is produced in the placenta [44], and that OPN is not transferred from the mother

Summary

Introduction

The dysregulation of B cell activation is prevalent during naturally acquired immunity against malaria. Sterile immunity against malaria is almost never achieved, individuals living in malaria endemic areas can acquire clinical immunity to severe forms of P. falciparum malaria [6, 7]. Naturally acquired immunity against blood stage parasites has been shown to involve both CD4+ T cells and antibodies [8, 9]. Numerous investigations have revealed that the quality, level, and breadth of the antibody response are important components of clinical immunity in malaria [11,12,13,14]. Primigravidae are at highest risk of P. falciparum pregnancy-associated malaria compared to multigravidae, and multiple pregnancies lead to the acquisition of antibodies against VAR2CSA, which reduces the prevalence and severity of infection [15, 16]

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