SLC11A1 is expressed in the human placenta across multiple gestational ages

Highlights

• Solute carrier family 11 member 1 (SLC11A1) is expressed in the human placenta.

• SLC11A1 expression is localized to the syncytiotrophoblast at multiple gestational ages.

• SLC11A1 may prevent infection of the placenta by certain intracellular pathogens.

Abstract

The human placenta functions as an innate immune barrier to prevent fetal infection. However, the molecular mechanisms accounting for placental resistance to pathogens are currently poorly understood. The solute carrier family 11 member 1 (SLC11A1) is a divalent cation transporter expressed primarily by macrophages and neutrophils that is essential for controlling infections by intracellular pathogens such as Salmonella, Leishmania and Mycobacteria. This report demonstrates that SLC11A1 is expressed in the syncytiotrophoblast of the human placenta at multiple gestational ages. These results suggest that SLC11A1 may play a role in blocking productive placental infections by certain intracellular pathogens.

Introduction

Pregnancy represents a significant window of susceptibility to pathogens, for infections cause severe complications that include miscarriage, preterm birth and congenital birth defects [1,2]. The human placenta has been proposed to serve as an innate immune barrier to infection in order to facilitate successful pregnancy. Indeed, previous studies demonstrated that the syncytiotrophoblast, the outer layer of the placenta in direct contact with maternal blood, is relatively resistant to infections by Toxoplasma gondii, Listeria monocytogenes and a wide variety of unrelated viruses [[3], [4], [5], [6], [7], [8]]. Although the human placenta expresses a number of different antimicrobial molecules, including toll like receptors, nucleotide-binding oligomerization domain proteins, defensins, inflammatory cytokines and their corresponding receptors, the precise mechanisms by which it defends against infections remain poorly defined [1,2].

SLC11A1 (also known as natural resistance associated macrophage protein-1/NRAMP-1) is a divalent cation transporter that is critical for controlling and clearing infections by intracellular pathogens such as Salmonella, Leishmania and Mycobacteria [[9], [10], [11]]. Defects in murine SLC11A1 and human SLC11A1 allelic variants are associated with host susceptibility to these pathogens [[9], [10], [11], [12], [13]]. Expression of SLC11A1 has primarily been observed in professional phagocytes such as M1 macrophages and neutrophils, but has also been reported in neurons and dendritic cells [[14], [15], [16], [17]]. Experimental evidence suggests that SLC11A1 functions to inhibit intracellular growth of select pathogens by restricting the availability of iron and magnesium ions, however, there is also experimental support for alternative modes of SLC11A1 action [9,10,[18], [19], [20]]. In this study, we investigated the expression of SLC11A1 in human placental villi from multiple gestational ages by RT-PCR and whole mount immunofluorescence (WMIF).