Increased HIV Target Cells and Decreased HLA Class I Expression at the Oral Mucosa is Associated with Mixed Feeding of Infants in Khayelitsha, South Africa
Methods: Oral mucosa samples were collected with a cytobrush from HIV-unexposed infants (either exclusively breast fed or mixed-fed) in Khayelitsha, South Africa at 6 and 14 weeks of age. The cells obtained from these samples were analyzed by flow cytometry (exclusively breastfed N=11, mixed-fed N=8), following staining with an amine-reactive live/dead marker, anti-CD45 and anti-CD4 antibodies. In addition, a transcriptomic analysis was performed (exclusively breastfed N=4, mixed-fed N=13), utilizing Nanostring technology, with further analysis by qPCR.
Results: At 6 weeks of age, no significant difference was observed in the percentage of HIV target cells (CD45+CD4+) in the oral mucosa of mixed and exclusively breastfed infants by flow cytometry. However, at 14 weeks of age, the oral mucosa of mixed-fed infants had a significantly higher percentage of HIV target cells compared to infants that were exclusively breastfed (p=0.01). In addition, transcript levels of a total of 50 immune factors, including IL-18, IL-7R, and multiple members of the caspase and keratin families, were modulated in the oral mucosa of mixed-fed infants. Particularly intriguing is a decrease in HLA class I expression in mixed-fed compared to exclusively breastfed infants.
Conclusion: These data suggest that the increased HIV susceptibility of mixed-fed infants may be mediated by an increase in HIV-susceptible cells at the first site of viral exposure, and a decrease in expression of HLA class I proteins that may impair T cell mediated anti-viral responses at the oral mucosa. Understanding the mechanism of increased HIV susceptibility in mixed-fed infants may inform interventions to prevent HIV transmission across mucosal surfaces.
H. Jaspan, None
D. Sodora, None
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