Type III Interferons in Antiviral Defenses at Barrier Surfaces

Abstract

Barrier surfaces such as the epithelium lining the respiratory and gastrointestinal (GI) tracts, the endothelium comprising the blood-brain barrier (BBB), and placental trophoblasts provide key physical and immunological protection against viruses. These barriers utilize nonredundant mechanisms to suppress viral infections including the production of interferons (IFNs), which induce a strong antiviral state following receptor binding. However, whereas type I IFNs control infection systemically, type III IFNs (IFN-λs) control infection locally at barrier surfaces and are often preferentially induced by these cells. In this review we focus on the role of IFN-λ at barrier surfaces, focusing on the respiratory and GI tracts, the BBB, and the placenta, and on how these IFNs act to suppress viral infections.

Keywords: barrier surfaces; innate immunity; interferon; placenta.

Figure 1:. Protective cellular barriers of the human body.

The cell composition of the blood-brain barrier, respiratory tract, gastrointestinal tract, and placenta are shown. The blood-brain barrier is made up in part of microvascular endothelial cells which form a physical barrier between the brain and the blood. The respiratory epithelium is composed of epithelial cells and goblet cells, which secrete mucus. The respiratory epithelial cells have cilia which beat in concert to clear mucus. The gastrointestinal tract contains enterocytes which have microvilli and goblet cells which secrete mucus. The human placenta is composed in part by the outermost syncytiotrophoblasts and inner cytotrophoblasts. Syncytiotrophoblasts form a dense brush border, but unlike the respiratory and GI epithelium, does not contain junctional complexes between cells (as the syncytium is a continuous layer).

Figure 2:. Human placental Structure.

A zoomed in villous tree shows floating and anchoring villi. The villous trees are lined by syncytiotrophoblasts and an inner layer of cytotrophoblasts (that become more discontinuous throughout pregnancy) that fuse to replenish the outer syncytial layer. Invasive extravillous trophoblasts extend from the villous tree into the maternal decidua and both anchor the placenta to the uterine wall and remodel the maternal microvasculature.

Figure 3:. Syncytiotrophoblasts constitutively release IFN-λs.

Fetal derived syncytiotrophoblasts constitutively release IFN-λs that lead to the upregulation of ISGs in both autocrine (in the syncytium itself) and paracrine (presumably in maternal-derive tissue) manners.