Regulation of Retroviral Infections / Research / Research groups / Control of HIV-1 mother-to-child transmission

Unité de Régulation des Infections Rétrovirales

Control of HIV-1 mother-to-child transmission


THE INNATE MUCOSAL IMMUNITY IN THE CONTROL OF HIV-1 TRANSMISSION AT THE MATERNO-FETAL INTERFACE

Hicham El-Costa, PhD, postdoctoral fellow
Héloïse Quillay, PhD student
Marie-Thérèse Nugeyre, Engineer IP
Claude Cannou, Technician, IP


Despite a close contact between infected maternal cells and the placenta during human pregnancy, there is paradoxically, even in absence of antiretroviral therapy, a low frequency of early in utero mother-to-child transmission (MTCT) of HIV-1. Most of the transmission occurs during the last trimester of pregnancy and during delivery. Our group is interested in understanding the mechanisms involved in this natural control of HIV-1 transmission.
We have previously shown that in contrast to the resistance of placental trophoblast cells to cell-free virus infection, cell-to-cell contact between infected maternal cells and the trophoblast in vitro leads to a selective viral passage through the trophoblast layer. The anti/pro-inflammatory placental cytokine balance as well as co-infections such as Plasmodium falciparum are involved in the regulation of HIV-1 in utero MTCT.
During pregnancy, the placenta interacts directly with maternal blood cells but also with cells from the maternal uterine mucosa (decidual cells). We have shown that the decidua could be a source of infected cells and that CD14+ antigen presenting cells (CD14+ dAPC) are the main targets of HIV-1 infection.
The presence of HIV-1 target cells in the decidua in vitro and the low rate of in utero MTCT during the first trimester of pregnancy suggest that a natural control occurs in vivo limiting cell-to-cell infection of the placenta and consequently the infection of the fetus. We are currently investigating the role of the maternal innate immunity in this control and more specifically of decidual NK (dNK) cells that are highly represented in this tissue. The receptor repertoire of dNK cells is distinct from the one of the periphery and evolved during the first trimester of pregnancy. Decidual soluble factors inhibit partially decidual mononuclear cell infection. The natural control of in utero transmission might involve soluble factors together with dAPC/dNK cell interactions. The dynamics of the dNK repertoire suggests different mechanisms of control according to the time of the pregnancy. The decidua is a relevant model to identify innate immune correlates of protection against HIV-1 infection in a mucosa, preferential site for viral entry in the body.
In parallel, we are starting a pilot study aiming to characterize APC and NK cells in the human female reproductive tract (FRT) to analyse the role of their interactions in the regulation of HIV-1 transmission within the FRT.