Abstract
Maternal factors and exposure to pathogens have an impact on infant health. For instance, HIV exposed but uninfected infants have higher morbidity and mortality than HIV unexposed infants. Innate responses are the first line of defense and orchestrate the subsequent adaptive immune response and are especially relevant in newborns. To determine the association of maternal HIV infection with maternal and newborn innate immunity we analyzed the cytokine responses upon pattern recognition receptor (PRR) stimulations in the triad of maternal peripheral and placental blood as well as in cord blood in a cohort of mother-infant pairs from southern Mozambique. A total of 48 women (35 HIV-uninfected and 13 HIV-infected) were included. Women and infant innate responses positively correlated with each other. Age, gravidity and sex of the fetus had some associations with spontaneous production of cytokines in the maternal peripheral blood. HIV-infected women not receiving antiretroviral therapy (ART) before pregnancy showed decreased IL-8 and IL-6 PRR responses in peripheral blood compared to those HIV-uninfected, and PRR hyporesponsiveness for IL-8 was also found in the corresponding infant’s cord blood. HIV infection had a greater impact on placental blood responses, with significantly increased pro-inflammatory, TH1 and TH17 PRR responses in HIV-infected women not receiving ART before pregnancy compared to HIV-uninfected women. In conclusion, innate response of the mother and her newborn was altered by HIV infection in the women who did not receive ART before pregnancy. As these responses could be related to birth outcomes, targeted innate immune modulation could improve maternal and newborn health.
Highlights
There were 2.5 million estimated deaths in children within the first month of life in 2017 (WHO, 2017), mostly in low-income countries
Given the unique access to the triad of maternal peripheral and placental blood as well newborn cord blood, we were able to identify that the relationship of maternal HIV-infection with cytokine responses was predominantly evident in the placental blood compartment
Our study design allowed us to identify that this impact of HIV on maternal and newborn innate immunity was restricted to women who had not received antiretroviral therapy (ART) before pregnancy
Summary
There were 2.5 million estimated deaths in children within the first month of life in 2017 (WHO, 2017), mostly in low-income countries. Children born to HIV-infected mothers, but not themselves infected, suffer higher morbidity and mortality (Slogrove et al, 2012, 2017; Moraleda et al, 2014; Rupérez et al, 2017; Goetghebuer et al, 2018) This is a high concern for public health since the successful implementation of measures to prevent mother-tochild transmission of HIV has resulted in a reduced incidence of pediatric HIV, but an increase in the number of HIV-exposed uninfected (HEU) infants, in sub-Saharan Africa. Biological causes behind the increased morbidity and mortality in HEU include, lower transfer of maternal antibodies to newborns, alterations in the immune system of infants due to exposure to antiretroviral drugs, the immune activation in the mother driven by the infection and HIV exposure in utero (Ruck et al, 2016). Adverse birth outcomes in HEU such as prematurity (Et et al, 2004; Chen et al, 2012) and fetal anemia (González et al, 2017) may negatively affect the newborn’s health outcomes
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