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Placental Hofbauer cells limit HIV-1 replication and potentially offset mother to child transmission (MTCT) by induction of immunoregulatory cytokines

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...

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Autores principales: Johnson, Erica L, Chakraborty, Rana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3524025/
https://www.ncbi.nlm.nih.gov/pubmed/23217137
http://dx.doi.org/10.1186/1742-4690-9-101
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author Johnson, Erica L
Chakraborty, Rana
author_facet Johnson, Erica L
Chakraborty, Rana
author_sort Johnson, Erica L
collection PubMed
description 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-1(BaL). 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. CONCLUSION: HCs have reduced ability to replicate and disseminate R5-tropic HIV-1(BaL)in 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.
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spelling pubmed-35240252012-12-18 Placental Hofbauer cells limit HIV-1 replication and potentially offset mother to child transmission (MTCT) by induction of immunoregulatory cytokines Johnson, Erica L Chakraborty, Rana Retrovirology Research 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-1(BaL). 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. CONCLUSION: HCs have reduced ability to replicate and disseminate R5-tropic HIV-1(BaL)in 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. BioMed Central 2012-12-05 /pmc/articles/PMC3524025/ /pubmed/23217137 http://dx.doi.org/10.1186/1742-4690-9-101 Text en Copyright ©2012 Johnson and Chakraborty; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Johnson, Erica L
Chakraborty, Rana
Placental Hofbauer cells limit HIV-1 replication and potentially offset mother to child transmission (MTCT) by induction of immunoregulatory cytokines
title Placental Hofbauer cells limit HIV-1 replication and potentially offset mother to child transmission (MTCT) by induction of immunoregulatory cytokines
title_full Placental Hofbauer cells limit HIV-1 replication and potentially offset mother to child transmission (MTCT) by induction of immunoregulatory cytokines
title_fullStr Placental Hofbauer cells limit HIV-1 replication and potentially offset mother to child transmission (MTCT) by induction of immunoregulatory cytokines
title_full_unstemmed Placental Hofbauer cells limit HIV-1 replication and potentially offset mother to child transmission (MTCT) by induction of immunoregulatory cytokines
title_short Placental Hofbauer cells limit HIV-1 replication and potentially offset mother to child transmission (MTCT) by induction of immunoregulatory cytokines
title_sort placental hofbauer cells limit hiv-1 replication and potentially offset mother to child transmission (mtct) by induction of immunoregulatory cytokines
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3524025/
https://www.ncbi.nlm.nih.gov/pubmed/23217137
http://dx.doi.org/10.1186/1742-4690-9-101
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