Inhibition of DC-SIGN-mediated transmission of human immunodeficiency virus type 1 by Toll-like receptor 3 signalling in breast milk macrophages.
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.
Yagi
Yukie
Y
Department of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan.
Watanabe
Eri
E
Watari
Eiji
E
Shinya
Eiji
E
Satomi
Misao
M
Takeshita
Toshiyuki
T
Takahashi
Hidemi
H
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
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
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