title: Inhibition of DC-SIGN-mediated transmission of human immunodeficiency virus type 1 by Toll-like receptor 3 signalling in breast milk macrophages.
abstract: The majority of cells in early/colostrum milk are breast milk macrophages (BrMMø) expressing dendritic cell (DC)-specific intercellular adhesion molecule 3 (ICAM3) grabbing nonintegrin (DC-SIGN), and the expression level of DC-SIGN on BrMMø will determine cell-to-cell human immunodeficiency virus type 1 (HIV-1) transmissibility. Thus, one of the strategies to prevent vertical transmission of HIV-1 through breast-feeding is to find a way to suppress DC-SIGN expression on BrMMø. As for the expression of Toll-like receptors (TLRs) in BrMMø, TLR3 was always seen in BrMMø but not in peripheral blood monocytes (PBMo). Also, the expression of TLR3 was slightly enhanced in BrMMø when the cells were treated with interleukin (IL)-4. Moreover, when TLR3 was stimulated with its specific ligand, the double-stranded RNA (dsRNA) poly(I:C), DC-SIGN expression on BrMMø was reduced even in the IL-4-mediated enhanced state. Some reduction may be caused by type I interferons (IFNs), such as IFN-alpha/beta, secreted from BrMMø. Indeed, both IFNs, particularly IFN-beta, showed a strong capacity to suppress the enhancement of DC-SIGN expression on IL-4-treated BrMMø and such TLR3-mediated DC-SIGN suppression was partially abrogated by the addition of anti-IFN-alpha/beta-receptor-specific antibodies. As expected, DC-SIGN-mediated HIV-1 transmission to CD4-positive cells by BrMMø was inhibited by either poly(I:C) stimulation or by treatment with type I IFNs. These findings suggest a possible strategy for preventing mother-to-child transmission (MTCT) of HIV-1 via breast-feeding through TLR3 signalling.
authors.affiliation: Department of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Yagi
authors.forename: Eri
authors.initials: E
authors.lastname: Watanabe
authors.forename: Eiji
authors.initials: E
authors.lastname: Watari
authors.forename: Eiji
authors.initials: E
authors.lastname: Shinya
authors.forename: Misao
authors.initials: M
authors.lastname: Satomi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takeshita
authors.forename: Hidemi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D015815:Cell Adhesion Molecules / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism; D016899:Interferon-beta / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000276:immunology*; D008024:Ligands; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008895:Milk, Human / Q000276:immunology*; D011070:Poly I-C / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology*; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D016898:Interferon-alpha; D016899:Interferon-beta; D037181:Lectins, C-Type; D008024:Ligands; D011070:Poly I-C; D011956:Receptors, Cell Surface; D051196:Toll-Like Receptor 3; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C495344:TLR3 protein, human
references.citation: Virology. 2003 Sep 1;313(2):343-53
references.pmid: 12954203
references.citation: J Acquir Immune Defic Syndr. 2009 Jun 1;51(2):117-24
references.pmid: 19346967
references.citation: Immunology. 2003 Feb;108(2):189-95
references.pmid: 12562327
references.citation: Blood. 2003 Oct 1;102(7):2660-9
references.pmid: 12829592
references.citation: J Infect Dis. 2005 Jan 15;191(2):174-81
references.pmid: 15609226
references.citation: Cell. 2000 Mar 3;100(5):587-97
references.pmid: 10721995
references.citation: J Acquir Immune Defic Syndr. 2007 Dec 15;46(5):651-4
references.pmid: 18043320
references.citation: J Cell Sci. 2004 Jul 15;117(Pt 16):3435-45
references.pmid: 15213252
references.citation: J Virol. 2007 Jul;81(14):7559-70
references.pmid: 17475656
references.citation: Int J Med Sci. 2008 Jan 04;5(1):1-8
references.pmid: 18219369
references.citation: Biochem Biophys Res Commun. 2003 Jul 4;306(3):674-9
references.pmid: 12810071
references.citation: Ann N Y Acad Sci. 2000 Nov;918:156-62
references.pmid: 11131699
references.citation: J Virol. 1995 Jun;69(6):3949-54
references.pmid: 7745752
references.citation: Virology. 2004 Aug 15;326(1):79-89
references.pmid: 15262497
references.citation: Nature. 2001 Oct 18;413(6857):732-8
references.pmid: 11607032
references.citation: J Infect Dis. 1998 Jan;177(1):34-9
references.pmid: 9419167
references.citation: J Virol. 2008 Aug;82(15):7613-23
references.pmid: 18508883
references.citation: J Virol. 1995 May;69(5):3216-9
references.pmid: 7707554
references.citation: Curr Opin Infect Dis. 2006 Feb;19(1):33-8
references.pmid: 16374215
references.citation: J Infect Dis. 2003 Mar 1;187(5):741-7
references.pmid: 12599047
references.citation: Int Immunol. 2004 Jan;16(1):55-63
references.pmid: 14688061