Decidual soluble factors participate in the control of HIV-1 infection at the maternofetal interface

Romain Marlin,Claude Cannou,Nadia Berkane,Elisabeth Menu,Marion Duriez,Marie-Thérèse Nugeyre,Anne Le Breton,Françoise Barré-Sinoussi

doi:10.1186/1742-4690-8-58

Romain Marlin, Claude Cannou + Show 6 more

Open Access

https://doi.org/10.1186/1742-4690-8-58

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Abstract

BackgroundMaternofetal transmission (MFT) of HIV-1 is relatively rare during the first trimester of pregnancy despite the permissivity of placental cells for cell-to-cell HIV-1 infection. Invasive placental cells interact directly with decidual cells of the uterine mucosa during the first months of pregnancy, but the role of the decidua in the control of HIV-1 transmission is unknown.ResultsWe found that decidual mononuclear cells naturally produce low levels of IL-10, IL-12, IL-15, TNF-α, IFN-α, IFN-γ and CXCL-12 (SDF-1), and large amounts of CCL-2 (MCP1), CCL-3 (MIP-1α), CCL-4 (MIP-1β), CCL-5 (Rantes), CXCL-10 (IP-10), IL-6 and IL-8. CCL-3 and CCL-4 levels were significantly upregulated by in vitro infection with R5 HIV-1 but not X4. Decidual CD14+ antigen presenting cells were the main CCL-3 and CCL-4 producers among decidual leukocytes. R5 and X4 HIV-1 infection was inhibited by decidual cell culture supernatants in vitro. Using HIV-1 pseudotypes, we found that inhibition of the HIV-1 entry step was inhibited by decidual soluble factors.ConclusionOur findings show that decidual innate immunity (soluble factors) is involved in the control of HIV-1 infection at the maternofetal interface. The decidua could thus serve as a mucosal model for identifying correlates of protection against HIV-1 infection.

Highlights

Maternofetal transmission (MFT) of Human Immunodeficiency Virus type 1 (HIV-1) is relatively rare during the first trimester of pregnancy despite the permissivity of placental cells for cell-to-cell HIV-1 infection
Some chemokines inhibit HIV-1 entry by competitive binding to viral co-receptors [3,4]: CCL-3, CCL-4 and CCL-5 interact with the CCR5 coreceptor, thereby inhibiting the entry of R5 HIV-1, while CXCL-12 binds to CXCR4 and inhibits X4 HIV-1 entry
Flow cytometry analyzes show that both leukocytes (CD45+) and non-leukocytes (CD45-) cells were present in decidual mononuclear cells and that dNK cells are the main leukocyte population

Summary

Introduction

Maternofetal transmission (MFT) of HIV-1 is relatively rare during the first trimester of pregnancy despite the permissivity of placental cells for cell-to-cell HIV-1 infection. Invasive placental cells interact directly with decidual cells of the uterine mucosa during the first months of pregnancy, but the role of the decidua in the control of HIV-1 transmission is unknown. Cytokines and chemokines can interfere with several steps of the Human Immunodeficiency Virus type 1 (HIV-1) replicative cycle. Proinflammatory cytokines such as IL-6, IL-12 and TNF-a stimulate HIV-1 replication by promoting inflammation or proviral genome transcription [5,6,7]. Cytokines are involved in physiological processes, for example regulating blastocyst implantation during the first trimester of pregnancy [8], as well as placental invasion [9] and tolerance of the fetus [10]

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