Author:
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Dobaño, Carlota, 1969-; Berthoud, Tamara; Manaca, Maria Nelia; Nhabomba, Augusto; Guinovart, Caterina; Aguilar, Ruth; Barbosa, Arnoldo; Groves, Penny; Rodríguez, Mauricio H.; Jiménez, Alfons; Quimice, Lazaro M.; Aponte, John J.; Ordi i Majà, Jaume; Doolan, Denise L.; Mayor Aparicio, Alfredo Gabriel; Alonso, Pedro
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Abstract:
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BACKGROUND: Increased susceptibility to malaria during pregnancy
is not completely understood. Cellular immune responses mediate
both pathology and immunity but the effector responses involved
in these processes have not been fully characterized. Maternal
and fetal cytokine and chemokine responses to malaria at
delivery, and their association with pregnancy and childhood
outcomes, were investigated in 174 samples from a mother and
child cohort from Mozambique. Peripheral and cord mononuclear
cells were stimulated with Plasmodium falciparum lysate and
secretion of IL-12p70, IFN-gamma, IL-2, IL-10, IL-8, IL-6, IL-4,
IL-5, IL-1beta, TNF, TNF-beta was quantified in culture
supernatants by multiplex flow cytometry while cellular mRNA
expression of IFN-gamma, TNF, IL-2, IL-4, IL-6, IL-10 and IL-13
was measured by quantitative PCR. RESULTS: Higher concentrations
of IL-6 and IL-1beta were associated with a reduced risk of P.
falciparum infection in pregnant women (p < 0.049).
Pro-inflammatory cytokines IL-6, IL-1beta and TNF strongly
correlated among themselves (rho > 0.5, p < 0.001). Higher
production of IL-1beta was significantly associated with
congenital malaria (p < 0.046) and excessive TNF was
associated with peripheral infection and placental lesions (p
< 0.044). CONCLUSIONS: Complex network of immuno-pathological
cytokine mechanisms in the placental and utero environments
showed a potential trade-off between positive and negative
effects on mother and newborn susceptibility to infection. |