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

Background: Eotaxin-1 concentration in plasma has 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 319 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 concentration. 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 concentration in plasma showed a weak positive correlation with eotaxin-1 (rho =0.25, p < 0.05) and eotaxin-3 (rho= 0.35, p < 0.05) concentrations. Eotaxin-2 and 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 (rho Eo2 = - 0.28 p= 0.038, rho Eo3 = - 0.37 p= 0.011), and eotaxin-3 was negatively correlated with PfDBL3x-IgG levels (rho Eo3 = - 0.36 p= 0.011). Negative correlations of eotaxin-2 and 3 in plasma were also observed with atypical memory B cells (rho Eo2 = -0.37 p<0.001 and rho Eo3= -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 concentration and Plasmodium infection (β= -0.283, 95% CI: -0.601; 0.035, p = 0.079). Moreover, eotaxin-2 placental concentrations were significantly increased compared to peripheral concentrations in the malaria-exposed 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, further research is required to understand the role of these chemokines in this disease and in combination with pregnancy.