title: Placental Hofbauer cells limit HIV-1 replication and potentially offset mother to child transmission (MTCT) by induction of immunoregulatory cytokines.
abstract: BACKGROUND
  Despite readily detectable levels of the HIV-1 (co)-receptors CD4, CCR5 and DC-SIGN on placental macrophages (Hofbauer Cells [HCs]), the rate of HIV-1 infection in utero in the absence of interventions is only 7% of exposed infants. Here, we examine the replication kinetics of human HCs to the primary isolate HIV-1BaL. We also determined the infectivity of HIV-1-exposed HCs by co-culturing with isolated cord and peripheral blood mononuclear cells [CBMCs, PBMCs]. To understand the limiting nature of HCs to HIV-1 replication, we examined the effect of endogenously secreted cytokines on replication kinetics.
  
  
  RESULTS
  HCs have reduced ability to replicate HIV-1 in vitro (p < 0.01) and to transmit virus to CBMCs and PBMCs (p < 0.001 for both) compared to standard infections of MDMs. HCs were shown to release HIV-1 particles at levels comparable to MDMs, however exhibit significant decreases in viral transcription (gag and env), which may account for lower levels of HIV-1 replication. Un-stimulated HCs constitutively express significantly higher levels of regulatory cytokines, IL-10 and TGF-β, compared to MDMs (p < 0.01), which may contribute to immunoregulatory predominance at the placenta and possibly account for down-regulation of HIV-1 replication and infectivity by HCs. We further demonstrate that these regulatory cytokines inhibit HIV-1 replication within HCs in vitro.
  
  
  CONCLUSIONS
  HCs have reduced ability to replicate and disseminate R5-tropic HIV-1BaLin vitro and potentially offset mother to child transmission (MTCT) of HIV-1 by the induction of immunoregulatory cytokines. Despite the potential for migration and infectivity, HCs are not present in the neighboring fetal circulation. These results implicate HCs as important mediators of protection at the feto-maternal interface during ongoing HIV-1 exposure.
authors.affiliation: Department of Pediatrics and Children's Healthcare of Atlanta, Emory University, Atlanta, GA 30322, USA.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Johnson
authors.forename: Rana
authors.initials: R
authors.lastname: Chakraborty
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000635:transmission*; D002462:Cell Membrane / Q000821:virology; D054405:Chemokine CCL3 / Q000502:physiology; D054407:Chemokine CCL4 / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008264:Macrophages / Q000502:physiology*; D010920:Placenta / Q000166:cytology / Q000821:virology*; D011247:Pregnancy; D019713:Receptors, CCR5 / Q000502:physiology; D019065:Virus Assembly; D014779:Virus Replication
chemical_list: C515429:CCL3 protein, human; C066507:CCL4 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines; D019713:Receptors, CCR5