Transmission of macrophage-tropic HIV-1 by breast-milk macrophages via DC-SIGN.
Recent findings suggest that macrophage-tropic human immunodeficiency virus type 1 (HIV-1) produced in colostrum/early breast milk may hold a clue to determine the mechanisms of transmission of HIV-1 via breast-feeding. Here, we show that the majority of CD4(+) cells in the colostrum are CD14(+) macrophages expressing both chemokine receptors and DC-SIGN, a dendritic cell-specific receptor for HIV-1. The R5-type macrophage-tropic HIV-1 isolate NL(AD8) infected such breast-milk macrophages and caused them to secrete virus particles efficiently; however, the secreted virions showed only a weak transmissibility to their susceptible target, MAGIC-5 cells. When stimulated with interleukin-4, the breast-milk macrophages demonstrated a striking enhancement of expression of DC-SIGN and showed a strong capacity to transmit NL(AD8) virions to MAGIC-5 cells, which was specifically blocked by anti-DC-SIGN-specific antibody. These results suggest that HIV-1 virions captured by DC-SIGN, but not secreted cell-free virions, may be more efficiently transmitted to other compartments, such as the gastrointestinal tract, through acidic gastric juice.
Satomi
Misao
M
Department of Microbiology and Immunology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
Shimizu
Masumi
M
Shinya
Eiji
E
Watari
Eiji
E
Owaki
Atsuko
A
Hidaka
Chizuno
C
Ichikawa
Masao
M
Takeshita
Toshiyuki
T
Takahashi
Hidemi
H
D000328:Adult; D000918:Antibody Specificity; D015704:CD4 Antigens / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002461:Cell Line, Transformed; D005260:Female; D015658:HIV Infections / Q000378:metabolism / Q000635:transmission*; D015497:HIV-1 / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D037181:Lectins, C-Type / Q000502:physiology*; D008264:Macrophages / Q000821:virology*; D008895:Milk, Human / Q000166:cytology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015704:CD4 Antigens; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin