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INNATE IMMUNE ACTIVATION AMONG HIV-1 EXPOSED UNINFECTED INFANTS FROM BOTSWANA
Pilar Garcia Broncano1, Samuel W. Kgole2, Gosego Masasa2, Terence Mohammed2, Sikhulile Moyo2, Joseph Makhema2, Xu G. Yu1, Jennifer Jao3, Roger L. Shapiro4, Mathias Lichterfeld5, Kathleen M. Powis6
1Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA,2Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana,3Icahn School of Medicine at Mt Sinai, New York, NY, USA,4Harvard University, Boston, MA, USA,5Brigham and Women's Hospital, Boston, MA, USA,6Massachusetts General Hospital, Boston, MA, USA
HIV-exposed uninfected (HEU) infants continue to experience increased morbidity/mortality from infectious causes compared with infants born to HIV-uninfected women. To explore possible immune etiologies, we conducted an immune profiles analysis, comparing profiles from a Botswana-based cohort of HEU to HIV-unexposed (HU) infants.
Multiparametric flow cytometry was used to quantify proportions and phenotypic characteristics of innate immune cells (monocytes, dendritic cells and NK cells) and adaptive T and B cell-mediated immune responses using peripheral blood mononuclear cells (PBMCs) collected at 3-months of life from HEU and HU infants enrolled in a longitudinal gut microbiome study in Botswana. All HIV-infected women received ≥6 weeks of ART prior to delivery. All infants were born full-term and all HEU infants tested HIV negative at 3 months of life.
Thirty-three infants (17 HEU and 16 HU) were studied cross-sectionally. HEU infants had lower proportions CD14+ monocytes compared with HU infants (p=0.013). The proportion of CD14+ CD16- 'classical' monocytes was significantly reduced in HEU infants, while proportions of CD14+ CD16+ non-classical/intermediate monocytes, associated with increased activation and inflammatory responses, were markedly increased (Figure). Proportions of NK cells, the primary innate immune system effector cell, were lower in HEU infants (p=0.026). Upregulation of NKp30, a surface marker denoting terminal activation, on CD56hiCD16low NK cell subset was noted among PBMCs of HEU infants. Frequencies of CD4+ and CD8+ T cell subsets, proportions of regulatory T cells and expression of immune activation markers on these T cell populations did not differ between groups. Proportion of late memory B cells (Bm5, IgD- CD38-) was lower in HEU infants (p=0.026). While fewer HEU infants exclusively breastfed through 3 months (71% vs 88%), the difference was not significant (p=0.40). Despite these findings, there was no significant difference in hospitalizations in the first year of life between the groups.
In this cohort, in utero exposure to HIV-1 and ART was associated with a distinct immunological profile characterized by increased immune activation in the innate immune system. Longitudinal evaluations are needed to determine whether abnormal innate immune activation among HEU has longer-term clinical consequences.