TY - JOUR
T1 - Cytokine signatures of Plasmodium vivax infection during pregnancy and delivery outcomes
AU - Dobaño, Carlota
AU - Bardají, Azucena
AU - Arévalo-Herrera, Myriam
AU - Martínez-Espinosa, Flor E
AU - Bôtto-Menezes, Camila
AU - Padilla, Norma
AU - Menegon, Michela
AU - Kochar, Swati
AU - Kochar, Sanjay Kumar
AU - Unger, Holger
AU - Ome-Kaius, Maria
AU - Rosanas-Urgell, Anna
AU - Malheiros, Adriana
AU - Castellanos, Maria Eugenia
AU - Hans, Dhiraj
AU - Desai, Meghna
AU - Casellas, Aina
AU - Chitnis, Chetan E
AU - Severini, Carlo
AU - Mueller, Ivo
AU - Rogerson, Stephen
AU - Menéndez, Clara
AU - Requena, Pilar
N1 - FTX; DOAJ; (CC0 1.0)
PY - 2020
Y1 - 2020
N2 - 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 (IL-10) 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.
AB - 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 (IL-10) 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.
KW - Adolescent
KW - Adult
KW - Cohort Studies
KW - Cytokines/blood
KW - Female
KW - Humans
KW - Infant, Newborn
KW - Interleukin-10/blood
KW - Interleukin-1beta/blood
KW - Malaria, Vivax/blood
KW - Male
KW - Plasmodium vivax/physiology
KW - Pregnancy
KW - Pregnancy Complications, Parasitic/blood
KW - Pregnancy Outcome
KW - Th2 Cells/immunology
KW - Young Adult
U2 - 10.1371/journal.pntd.0008155
DO - 10.1371/journal.pntd.0008155
M3 - A1: Web of Science-article
C2 - 32365058
SN - 1935-2727
VL - 14
JO - PLoS Neglected Tropical Diseases
JF - PLoS Neglected Tropical Diseases
IS - 5
M1 - e0008155
ER -