Eotaxin‑2 and eotaxin‑3 in malaria exposure and pregnancy

Abstract

Background: Eotaxin-1 concentrations in plasma have been inversely associated with malaria exposure, malaria infection and pregnancy, but the effect of these conditions on the levels of the related chemokines eotaxin-2 and eotaxin-3 remains unknown. Methods: Eotaxin-2 and -3 concentrations were measured in 310 peripheral or placental plasma samples from pregnant and non-pregnant individuals from Papua New Guinea (malaria-endemic country) and Spain (malaria-naïve individuals) with previous data on eotaxin-1 concentrations. Correlations between eotaxin concentrations were examined with the Spearman’s test. Differences in eotaxin concentrations among groups were evaluated with the Kruskal–Wallis or Mann Whitney tests. The pairwise Wilcoxon test was performed to compare eotaxin-2 concentration between peripheral and placental matched plasmas. Univariable and multivariable linear regression models were estimated to assess the association between eotaxins and Plasmodium infection or gestational age. Results: Eotaxin-2 concentrations in plasma showed a weak positive correlation with eotaxin-3 (rho = 0.35, p < 0.05) concentrations. Eotaxin-2 concentrations in the malaria-exposed non-pregnant group were significantly lower than the in the malaria-naive non-pregnant and the malaria-exposed pregnant groups. Eotaxin-3 plasma concentrations were lower in malaria-exposed than in non-exposed groups (p < 0.05), but no differences were found associated to pregnancy. Eotaxin-2 and eotaxin-3 plasma concentrations were negatively correlated with anti-Plasmodium IgG levels: PfDBL5ε-IgG ( rhoEo2 = − 0.35, p = 0.005; rhoEo3 =− 0.37, p = 0.011), and eotaxin-3 was negatively correlated with PfDBL3x-IgG levels ( rhoEo3 =− 0.36; p = 0.011). Negative correlations of eotaxin-2 and 3 in plasma were also observed with atypical memory B cells ( rhoEo2 = − 0.37, p < 0.001; rhoEo3= − 0.28, p = 0.006), a B cell subset expanded in malaria-exposed individuals. In addition, a borderline negative association was observed between eotaxin-3 concentrations and Plasmodium infection (adjusted effect estimate, β = − 0.279, 95% CI − 0.605; 0.047, p = 0.091). Moreover, eotaxin-2 placental concentrations were significantly increased compared to peripheral concentrations in the malariaexposed pregnant group whereas the contrary was observed in the non-exposed pregnant group (p < 0.005). Conclusion: Although a clear epidemiological negative association is observed between eotaxins concentrations and malaria exposure and/or infection, pregnancy may alter this association for eotaxin-2. Further research is required to understand the role of these chemokines in this disease and in combination with pregnancy.