Cytokine signatures of Plasmodium vivax infection during pregnancy and delivery outcomes
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PUBLIC LIBRARY SCIENCE
Fecha
2020Referencia bibliográfica
Dobaño C, Bardají A, Arévalo-Herrera M, Martínez-Espinosa FE, Bôtto-Menezes C, Padilla N, et al. (2020) Cytokine signatures of Plasmodium vivax infection during pregnancy and delivery outcomes. PLoS Negl Trop Dis 14(5): e0008155. [https://doi.org/10.1371/journal.pntd.0008155]
Patrocinador
European Union Seventh Framework Programme (FP7/2007-2013) 201588; Ministerio de Economia y Competitividad (National R&D Internationalization Programme, EUROSALUD 2008, Spain) EUS2009-03560; Centers for Disease Control and Prevention (CDC) Foundation; Malaria in Pregnancy Consortium (MiPc) - Bill & Melinda Gates Foundation 46099; MiPc; Spanish Government RYC-2008-02631; National Health and Medical Research Council of Australia GNT1043345Resumen
Plasmodium vivax malaria is a neglected disease, particularly during pregnancy. Severe
vivax malaria is associated with inflammatory responses but in pregnancy immune alterations make it uncertain as to what cytokine signatures predominate, and how the type and
quantity of blood immune mediators influence delivery outcomes. We measured the plasma
concentrations of a set of thirty-one biomarkers, comprising cytokines, chemokines and
growth factors, in 987 plasma samples from a cohort of 572 pregnant women from five
malaria-endemic tropical countries and related these concentrations to delivery outcomes
(birth weight and hemoglobin levels) and malaria infection. Samples were collected at
recruitment (first antenatal visit) and at delivery (periphery, cord and placenta). At recruitment, we found that P. vivax–infected pregnant women had higher plasma concentrations
of proinflammatory (IL-6, IL-1β, CCL4, CCL2, CXCL10) and TH1-related cytokines (mainly
IL-12) than uninfected women. This biomarker signature was essentially lost at delivery and
was not associated with birth weight nor hemoglobin levels. Antiinflammatory cytokines (IL10) were positively associated with infection and poor delivery outcomes. CCL11 was the
only biomarker to show a negative association with P. vivax infection and its concentration
at recruitment was positively associated with hemoglobin levels at delivery. Birth weight was
negatively associated with peripheral IL-4 levels at delivery. Our multi-biomarker multicenter
study is the first comprehensive one to characterize the immunological signature of P. vivax infection in pregnancy thus far. In conclusion, data show that while TH1 and pro-inflammatory responses are dominant during P. vivax infection in pregnancy, antiinflammatory cytokines may compensate excessive inflammation avoiding poor delivery outcomes, and
skewness toward a TH2 response may trigger worse delivery outcomes. CCL11, a chemokine largely neglected in the field of malaria, emerges as an important marker of exposure or
mediator in this condition.