Maternal HIV Exposure Is Associated With Transient Transcriptional Changes in Monocytes and Natural Killer Cells in Early Infancy.

BACKGROUND: Differences in immune responses and infectious disease have been described in children exposed to human immunodeficiency virus (HIV) but uninfected (CHEU), compared with children unexposed to HIV (CHU). We hypothesized that maternal HIV exposure modifies the transcriptome and epigenome of innate immune cells in CHEU that may contribute to dysregulation of antimicrobial immune responses. METHODS: Monocytes and natural killer (NK) cells were evaluated in peripheral blood mononuclear cells from CHEU and CHU in Kenya at 6-10 weeks and 12 months of age. Monocyte and NK cell subsets were evaluated by flow cytometry. Gene expression, chromatin accessibility, and DNA methylation were evaluated in classic monocytes and CD56dim NK cells. RESULTS: The frequency of monocyte and NK cell subsets did not differ significantly by maternal HIV exposure. We identified differentially expressed genes (DEGs) in monocytes (535 DEGs) and NK cells (191 DEGs) comparing CHEU and CHU at 6-10 weeks. Functional enrichment analysis indicated broad down-regulation of cytokine signaling, inflammatory activation, biosynthetic capacity, and metabolism genes in both monocytes and NK cells in early infancy among CHEU. Notably, minimal differences were observed in chromatin accessibility and DNA methylation at both time points. Differential gene expression decreased substantially by 12 months. CONCLUSIONS: Maternal HIV exposure modified the transcriptome of monocytes and NK cells in early infancy, with differential expression of genes involved in antimicrobial immune response pathways that largely resolved by 12 months. Future studies are warranted to determine whether these transient transcriptional modifications of innate immune cells in early infancy are associated with increased risk of infectious disease in CHEU.