Changes in the Immune Response during Pregnancy are Associated with Protection against Malaria Infection and Better Delivery Outcomes

The Journal of Immunology has published a study performed by Dr. Pilar Requena and led by Dr. Carlota Dobaño from ISGlobal, showing that pregnancy is associated with changes in the immune response in malaria endemic regions, and that these changes are associated with a protection against malaria infection and better delivery outcomes.

During pregnancy, the mother's immune system must tolerate the foetus but still protect against infections. Regulatory T cells (Treg), a special type of T lymphocytes, play a crucial role in maintaining foetal tolerance by migrating from the blood towards the placenta, where they secrete interleukin 10 (IL-10), an immune-suppressive mediator. IL-10 is also produced by other regulatory T cells, such as T double positive lymphocytes (Tdpos) that co-produce the pro-inflammatory cytokine IFNg, although the role of these cells during pregnancy has not been addressed. The authors speculated that alterations of regulatory T cell subsets during pregnancy could alter susceptibility to malaria. Thus, they studied the effect of pregnancy in the T cell populations of pregnant women living in a malaria-endemic area (Papua New Guinea) as compared to women living in a malaria-free country (Spain).

The authors confirmed that pregnancy is associated with a decrease in the frequency of circulating Treg in women from both countries, and that this was independent of malaria exposure. Pregnancy in Papua New Guinea was associated with a higher percentage of IFN-g producing lymphocytes (Tdpos and TH1), and elevated concentrations of pro-inflammatory cytokines in blood correlated with a lower risk of falciparum infection during pregnancy and higher birth weights. Curiously, this was accompanied by an increase in the production of anti-inflammatory IL-10 by Treg and other T cells, which correlated to a lower prevalence of falciparum infections and higher haemoglobin concentrations at delivery.

The results of this study suggest that an activated immune system during pregnancy may protect against malaria and other endemic infections, while the increase in the immune-suppressive IL-10 cytokine may contribute to the control of excessive inflammatory responses that may harm the foetus.

This study involved the participation of nine research centres and is part of a multicentre project called Pregvax, that follows 10,000 women from five countries and whose goal is to identify clinical and epidemiological features of Plasmodium infection during pregnancy. Pregvax is coordinated by Dr. Clara Menendez, director of the Maternal-Child Health initiative at ISGlobal, belongs to the Malaria in Pregnancy Consortium (MiPC) and is funded by the EU 7^th Framework Program (FP7), the Bill and Melinda Gates Foundation and the ‘Ministerio de Ciencia e Innovación' (MICINN).