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From the Department of Medicine,*
Division of Infectious
Diseases, Karolinska Institutet Huddinge University Hospital,
Stockholm, Sweden; the Department of
Pathology,
Baylor Collage of Medicine,
Houston, Texas; the Department of Obstetrics and
Gynecology,
Northwestern University Medical
School, Chicago, Illinois; the Department of
Immunology/Microbiology,§
Rush Medical College,
Chicago, Illinois; and the Department of
Pediatrics, Division of Infectious
Diseases, Children’s Memorial Hospital/Northwestern University Medical
School, Chicago, Illinois
The role of placenta in vertical transmission is not yet fully understood. A protective role of the placenta during gestation is suggested by the finding that caesarian sections reduce the risk of transmission of human immunodeficiency virus (HIV)-1 from mother to child three- to fourfold. Here we investigated whether the immunological milieu of the placenta might be important in HIV-1 transmission. In situ imaging of immunohistochemically stained placenta sections and reverse transcriptase-polymerase chain reaction demonstrated a fourfold increase in CCR5:CXCR4 expression ratio in placentae from transmitting women compared to placentae from nontransmitting women. This chemokine receptor repertoire was consistent with an up-regulation of interleukin-4 and interleukin-10 expression in placentae from nontransmitting placentae compared to transmitting placentae. In situ imaging demonstrated that CCR5 and CXCR4 were expressed on placental macrophages and lymphocytes but not in trophoblasts. Simultaneous immunofluorescence/ultrasensitive in situ hybridization for HIV-1 gag-pol mRNA revealed that HIV-1 infects primarily CXCR4-expressing cells in placentae from nontransmitting women whereas predominantly CCR5-expressing cells were infected in placentae from transmitting women. These data are consistent with transmission of a homogeneous population of nonsyncytium-inducing HIV-1 isolates that use CCR5 as co-receptor.
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