Mother-to-child HIV-1 transmission events are differentially impacted by breast milk and its components from HIV-1-infected women
Department of Medicine (Division of Gastroenterology), University of Alabama at Birmingham, Birmingham, AL, United States; Mucosal and Vaccine Research Program Colorado (MAVRC), University of Colorado Denver, Aurora, CO, United States; Department of Biological Sciences, Auburn University, Auburn, AL, United States; Denver Veterans Affairs Medical Center, Denver, CO, United States; Centers for Disease Control and Prevention, Atlanta, GA, United States; Makerere University, Johns Hopkins University Research Collaboration, Kampala, Uganda; Veterans Affairs Medical Center, Birmingham, AL, United States; Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO, United States
Breast milk is a vehicle of infection and source of protection in post-natal mother-to-child HIV-1 transmission (MTCT). Understanding the mechanism by which breast milk limits vertical transmission will provide critical insight into the design of preventive and therapeutic approaches to interrupt HIV-1 mucosal transmission. However, characterization of the inhibitory activity of breast milk in human intestinal mucosa, the portal of entry in postnatal MTCT, has been constrained by the limited availability of primary mucosal target cells and tissues to recapitulate mucosal transmission ex vivo. Here, we characterized the impact of skimmed breast milk, breast milk antibodies (Igs) and non-Ig components from HIV-1- infected Ugandan women on the major events of HIV-1 mucosal transmission using primary human intestinal cells and tissues. HIV-1-specific IgG antibodies and non-Ig components in breast milk inhibited the uptake of Ugandan HIV-1 isolates by primary human intestinal epithelial cells, viral replication in and transport of HIV-1- bearing dendritic cells through the human intestinal mucosa. Breast milk HIV-1-specific IgG and IgA, as well as innate factors, blocked the uptake and transport of HIV-1 through intestinal mucosa. Thus, breast milk components have distinct and complementary effects in reducing HIV-1 uptake, transport through and replication in the intestinal mucosa and, therefore, likely contribute to preventing postnatal HIV-1 transmission. Our data suggests that a successful preventive or therapeutic approach would require multiple immune factors acting at multiple steps in the HIV-1 mucosal transmission process.
immunoglobulin; immunoglobulin A; immunoglobulin antibody; immunoglobulin G; adult; antibody specificity; Article; breast milk; cell transport; child; clinical article; controlled study; dendritic cell; disease association; female; human; human cell; Human immunodeficiency virus 1; Human immunodeficiency virus 1 infection; immune response; intestine epithelium cell; intestine mucosa; molecular dynamics; nonhuman; virus identification; virus isolation; virus replication; virus transmission; young adult
AI083127, NIH, National Institutes of Health; AI083615, NIH, National Institutes of Health; AI093151, NIH, National Institutes of Health; AI106395, NIH, National Institutes of Health; AI41361, NIH, National Institutes of Health; DK064400, NIH, National In