Impact of maternal HIV exposure, feeding status, and microbiome on infant cellular immunity

Abstract

At least one-third of infants born in sub-Saharan Africa have been exposed to the effects of maternal HIV infection and antiretroviral treatment. Intrauterine HIV exposure is associated with increased rates of morbidity and mortality in children. Although the mechanisms responsible for poor infant health with HIV-1 exposure are likely to be multifactorial, we posit that the maternal environment during gestation and in the perinatal period results in altered infant immunity and is possibly the strongest contributing factor responsible for the disproportionally high infectious events among HIV-exposed infants who remain HIV uninfected. This review provides a synthesis of studies reporting the impact of intrauterine HIV exposure, feeding practices, and microbiota on immune ontogeny in the first year of life in HIV-exposed uninfected infants.

Keywords: HIV-exposed uninfected infants; breastfeeding; immune development; microbiota and infectious diseases.

FIGURE 1. Schematic representation of the suggested model illustrating the link among in utero HIV exposure, breastfeeding, and microbiota on the developing immune system.

The left panel shows in a healthy pregnancy, the MF balance is maintained by Hofbauer cells, dNK, and Tregs in the placenta. Abs are efficiently transferred from mother to child via the placenta and breast milk provide protection against invading pathogens. Breastfeeding infants receive a plethora of bioactive compounds in breast milk including HMO that influences establishment of beneficial microbiota and promotes development of the infant’s immune system. In HIV-infected mothers, who may be invariably taking ARV drugs, chronic immune activation in the mother creates an inflammatory environment resulting in likely dysregulation of MF immune balance. Mother to child transfer of proinflammatory cytokines and chemokines occurs via placenta and/or breast milk activating innate cells in infants and promoting an expansion of inflammatory T cells (Th17 for example). Transplacental passage of maternal Abs is also impaired resulting in few protective antibodies in the infant circulation. Furthermore, less fucosylated and glycosylated HMOs are passed via maternal breast milk resulting in lower gut microbiota diversity.