title: Mother-to-Child HIV-1 Transmission Events Are Differentially Impacted by Breast Milk and Its Components from HIV-1-Infected Women.
abstract: 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.
authors.affiliation: Department of Medicine (Division of Gastroenterology), University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Ruizhong
authors.initials: R
authors.lastname: Shen
authors.affiliation: Mucosal and Vaccine Research Program Colorado (MAVRC), University of Colorado Denver, Aurora, Colorado, United States of America.
authors.forename: Jenna
authors.initials: J
authors.lastname: Achenbach
authors.affiliation: Department of Biological Sciences, Auburn University, Auburn, Alabama United States of America.
authors.forename: Yue
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Mucosal and Vaccine Research Program Colorado (MAVRC), University of Colorado Denver, Aurora, Colorado, United States of America.
authors.forename: Jana
authors.initials: J
authors.lastname: Palaia
authors.affiliation: Mucosal and Vaccine Research Program Colorado (MAVRC), University of Colorado Denver, Aurora, Colorado, United States of America.|Denver Veterans Affairs Medical Center, Denver, Colorado, United States of America.
authors.forename: Jeremy T
authors.initials: JT
authors.lastname: Rahkola
authors.affiliation: Department of Medicine (Division of Gastroenterology), University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Heidi J
authors.initials: HJ
authors.lastname: Nick
authors.affiliation: Department of Medicine (Division of Gastroenterology), University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Lesley E
authors.initials: LE
authors.lastname: Smythies
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Michelle
authors.initials: M
authors.lastname: McConnell
authors.affiliation: The Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda.
authors.forename: Mary G
authors.initials: MG
authors.lastname: Fowler
authors.affiliation: Department of Medicine (Division of Gastroenterology), University of Alabama at Birmingham, Birmingham, Alabama, United States of America.|Veterans Affairs Medical Center, Birmingham, Alabama, United States of America.
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Smith
authors.affiliation: Mucosal and Vaccine Research Program Colorado (MAVRC), University of Colorado Denver, Aurora, Colorado, United States of America.|Denver Veterans Affairs Medical Center, Denver, Colorado, United States of America.
authors.forename: Edward N
authors.initials: EN
authors.lastname: Janoff
mesh_terms: D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000635:transmission*; D015497:HIV-1; D006801:Humans; D007113:Immunity, Innate; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D018445:Infectious Disease Transmission, Vertical; D007413:Intestinal Mucosa / Q000276:immunology / Q000821:virology*; D008895:Milk, Human / Q000276:immunology*; D014454:Uganda
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G