Association of Maternal Factors and HIV Infection With Innate Cytokine Responses of Delivering Mothers and Newborns in Mozambique

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, T H 1 and T H 17 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.

Maternal and neonatal immune response to SARS-CoV-2, IgG transplacental transfer and cytokine profile

“…Mothers carrying a male fetus had higher concentrations of EGF, IL-15 and IL-7 cytokines, and induced higher antibody levels against SARS-CoV-2 than those carrying a female, but IgG transfer to the fetus was less efficient in the first ones. Previous studies have shown that fetal sex influences maternal serum cytokine and antibody profiles ( 55 – 57 ). In the context of SARS-CoV-2 infection, a recent study has reported similar results to ours, and a more pronounced SARS-CoV-2-specific antibody glycosylation in mothers carrying a male fetus, which would explain the reduced transplacental transfer ( 58 ).…”

Distinct cytokine profiles in late pregnancy in Ugandan people with HIV

“…There is considerable overlap and crosstalk between Th1 and Th2 responses, limiting the utility of this dichotomy 41 . Unfortunately, we were also unable to measure cytokines in the placental blood compartment 29 .…”

“…Overall, we found weak correlations between cytokine concentrations in maternal and umbilical cord plasma, supporting the lack of active placental regulation of cytokine production in umbilical cord, compared to maternal, blood. However, a 2020 study of cytokine responses in laboratory-stimulated blood samples from Mozambican mother-infant pairs, both with and without HIV, found a positive correlation between maternal and infant responses, suggesting a stronger association between maternal and offspring responses outside of the in utero period 29 . Furthermore, they observed that HIV infection affected the placental blood response, resulting in significantly heightened pro-inflammatory, Th1, and Th17 responses in individuals with HIV who did not receive ART before pregnancy.…”

“…Despite this, we found minimal correlation on a per-cytokine basis. While previous studies have identified correlations between maternal and infant cytokine levels, the relationship between maternal and umbilical cord samples remains poorly characterized 29 and relationships between cytokine profiles in maternal peripheral blood, placental blood, and umbilical cord blood remain unclear 40 . Additionally, we collected limited data on maternal coinfections and inflammatory disorders that could potentially influence maternal cytokine production.…”

Determinants and outcomes of low birth weight among newborns at a tertiary hospital in Zambia: A retrospective cohort study

“…[ 6 ] Prominent among the theories is through the pro-inflammatory process induced by high levels of interleukin-2 (IL-2), IL-6, and tumor necrosis factor-alpha due to HIV infection. [ 7 ] Before introducing ART for the treatment of HIV, studies reported the link between HIV and LBW. [ 8 9 ] However, after the initiation of widespread ART, the effects of HIV infection on birth weight became more challenging to assess partly due to the differences in the timing of ART initiation, type of ART, and adherence challenges.…”