High production of pro-inflammatory cytokines by maternal blood mononuclear cells is associated with reduced maternal malaria but increased cord blood infection

Dobaño, Carlota, Berthoud, Tamara, Manaca, Maria Nelia, Nhabomba, Augusto, Guinovart, Caterina, Aguilar, Ruth, Barbosa, Arnoldo, Groves, Penny, Rodríguez, Mauricio H., Jimenez, Alfons, Quimice, Lazaro M., Aponte, John J., Ordi, Jaume, Doolan, Denise L., Mayor, Alfredo, and Alonso, Pedro L. (2018) High production of pro-inflammatory cytokines by maternal blood mononuclear cells is associated with reduced maternal malaria but increased cord blood infection. Malaria Journal, 17.

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Abstract

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-γ, IL-2, IL-10, IL-8, IL-6, IL-4, IL-5, IL-1β, TNF, TNF-β was quantified in culture supernatants by multiplex flow cytometry while cellular mRNA expression of IFN-γ, 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-1β were associated with a reduced risk of P. falciparum infection in pregnant women (p < 0.049). Pro-inflammatory cytokines IL-6, IL-1β and TNF strongly correlated among themselves (ρ > 0.5, p < 0.001). Higher production of IL-1β 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.

Item ID: 56627
Item Type: Article (Refereed Research - C1)
Keywords: malaria, P. falciparum, pregnancy, cytokines, immunity, pathology, cord
Copyright Information: © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licensesby/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomainzero/1.0/) applies to the data made available in this article, unless otherwise stated.
ISSN: 1475-2875
Funders: European Union Framework Program 6 (EU FP6), Spanish Ministry of Science and Innovation (MICINN), Insitituto de Salud Carlos III (ISCIII), Pfizer Australia, Spanish Agency for International Cooperation and Development (AECID)
Projects and Grants: EU FP6 STREP Project 18902, MICINN SAF2005-25642-E, MICINN SAF2008-00743, MICINN RYC-2008-02631, ISCIII A107190024, ISCIII CM04/00028, ISCIII CE10/021-I3SNS
Date Deposited: 11 Jan 2019 02:57
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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