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Transcriptome profiling of NK cells and Classical Monocytes from HIV exposed and unexposed children

ABSTRACT: Differences in morbidity, immune responses, growth and developmental outcomes have been described in children exposed to HIV but uninfected (CHEU), compared with children unexposed to HIV (CHU). In order to determine if there is a maternal imprinting on the immune system in children we profiled CD56dim NK cells and CD14+ classical monocytes isolated from the PBMC of children that were exposed in utero to HIV but ininfected (HEU) versus children non-infected with HIV and not exposed (HUU). The HEU group was additionaly stratified by those children who were maternally infected before or during pregnacy. These data begin to define the longtidinal effects of maternal HIV exposure on the innate immune system over the first year of life.

ORGANISM(S): Homo sapiens

PROVIDER: GSE343384 | GEO | 2026/08/24

REPOSITORIES: GEO

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Project description:The transplacental transfer of maternal IgG to the developing fetus is critical for infant protection against infectious pathogens in the first year of life. However, factors that modulate the transplacental transfer efficiency of maternal IgG that could be harnessed for maternal vaccine design remain largely undefined. HIV-infected women have impaired placental IgG transfer, yet the mechanism underlying this impaired transfer is unknown, presenting an opportunity to explore factors that contribute to the efficiency of placental IgG transfer. We measured the transplacental transfer efficiency of maternal HIV and other pathogen-specific IgG in historical U.S. (n=120) and Malawian (n=47) cohorts of HIV-infected mothers and their HIV58 exposed uninfected and HIV-infected infants. We then examined the role of maternal HIV disease progression, infant factors, placental Fc receptor expression, and IgG Fc region subclass and glycan signatures and their association with transplacental transfer efficiency of maternal antigen-specific IgG. We established 3 distinct phenotypes of placental IgG transfer efficiency in HIV-infected women, including: 1) efficient transfer of the majority of antigen-specific IgG populations; 2) generally poor IgG transfer phenotype that was strongly associated with maternal CD4+ T cell counts, hypergammaglobulinemia, and frequently yielded non-protective levels of vaccine-specific IgG; and 3) variable transfer of IgG across distinct antigen specificities. Interestingly, maternal IgG characteristics, such as binding to placentally expressed Fc receptors FcgRIIa and FcgRIIIa, IgG subclass frequency, and Fc region glycan profiles were associated with placental IgG transfer efficiency. These maternal IgG transplacental transfer determinants were distinct among different antigen-specific IgG populations. Our findings suggest that in HIV-infected women, both maternal disease progression and Fc region characteristics modulate the selective placental transfer of distinct IgG subpopulations, with implications for both the health of HIV-exposed uninfected infants and maternal vaccine design.

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Transcriptome profiling of NK cells and Classical Monocytes from HIV exposed and unexposed children

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