Program Schedule

642
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

Session: Oral Abstract Session: HIV Related Inflammation, Complications and Comorbidities
Friday, October 10, 2014: 10:45 AM
Room: The Pennsylvania Convention Center: 107-AB
Background: In Khayelitsha, as in many South African informal settlements, 25% of new mothers are HIV-infected, and 40% of HIV-infected infants acquire HIV through breast milk.  The common practice of feeding infants both breast milk and non-breast milk foods, known as mixed-feeding, increases an infant’s susceptibility to HIV by up to 11 fold.  We hypothesized that the increase in HIV susceptibility seen in mixed-fed infants is due to an increase in immune activation at the oral mucosa, the mucosal surface first encountered by HIV in breast milk.  

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. 

Lianna Wood1,2, Cosette Leciel2, Heather Jaspan, MD, PhD2,3 and Donald Sodora, PhD1,2, (1)Global Health, University of Washington, Seattle, WA, (2)Seattle BioMed, Seattle, WA, (3)Immunology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, South Africa

Disclosures:

L. Wood, None

C. Leciel, None

H. Jaspan, None

D. Sodora, None

Findings in the abstracts are embargoed until 12:01 a.m. EDT, Oct. 8th with the exception of research findings presented at the IDWeek press conferences.

Sponsoring Societies:

© 2014, idweek.org. All Rights Reserved.

Follow IDWeek