Cytokine signatures of plasmodium vivax infection during pregnancy and delivery outcomes

Dobaño, Carlota, Bardají, Azucena, Arévalo-Herrera, Myriam, Martínez-Espinosa, Flor E., Bôtto-Menezes, Camila, Padilla, Norma, Menegon, Michela, Kochar, Swati, Kochar, Sanjay Kumar, Unger, Holger, Ome-Kaius, Maria, Rosanas-Urgell, Anna, Malheiros, Adriana, Castellanos, Maria Eugenia, Hans, Dhiraj, Desai, Meghna, Casellas, Aina, Chitnis, Chetan E., Severini, Carlo, Mueller, Ivo, Rogerson, Stephen, Menéndez, Clara, and Requena, Pilar (2020) Cytokine signatures of plasmodium vivax infection during pregnancy and delivery outcomes. PLoS Neglected Tropical Diseases, 14 (5). e0008155.

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Abstract

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.

Item ID: 75310
Item Type: Article (Research - C1)
ISSN: 1935-2735
Copyright Information: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Date Deposited: 13 Jul 2022 00:05
FoR Codes: 42 HEALTH SCIENCES > 4202 Epidemiology > 420207 Major global burdens of disease @ 100%
SEO Codes: 20 HEALTH > 2005 Specific population health (excl. Indigenous health) > 200509 Women's and maternal health @ 100%
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