Host–Viral Interactions in the Pathogenesis of Ulcerative Colitis

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  Figure 1. Colon epithelium. The deeper colonic mucosa is separated from the environment by a single layer of intestinal epithelial cells (IECs) constituting a physical and functional barrier. The IECs originate from the crypt base stem cells, which divide to give rise to more proliferative daughter cells. Most daughter IECs move upwards along the crypt and differentiate owing to a decreasing gradient of growth factors. IECs that reach the tip of the crypt undergo apoptosis and are then shed to the lumen. This entire cycle typically lasts 4–5 days. Throughout this migration, IECs differentiate into absorptive enterocytes, mucus-producing goblet cells, hormone-secreting enteroendocrine cells, tuft cells, or deep crypt secretory cells. A firm inner mucus layer reduces exposure to microorganisms. Intraepithelial lymphocytes (IELs), B cells, IgA-producing plasma cells, macrophages, and T cells reside in the lamina propria, contributing to and maintaining a hyporesponsive state. The microbiota may engage Pattern Recognition Receptors (PRRs) expressed on the IECs and may induce innate immune responses [6,7,8]. Mucins are the primary organic components of mucus, the properties of which are…

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  Figure 2. Schematic overview of PRRs involved in the sensing of viral infections in IECs. All TLRs share a common structure and signal through adaptor proteins. The elicited signaling pathway depends on the combination of TLRs and PAMPs. TLR2 and 4 recognize viruses at the cell surface, while TLR3 recognizes double-stranded (ds)RNA and TLR7 and 8 recognize single-stranded (ss)RNA, and TLR9 recognizes DNA with Unmethylated cytosine–guanine dinucleotide (CpG) motifs in the endosomes. Although it is not fully understood why, TLR3, TLR7, and TLR9 may occur both in the cell membrane and intracellularly [47]. TLRs may, in addition to apical and endosomal, include basolateral and basal cell membrane expression. All TLRs, except TLR3, utilize myeloid differentiation factor 88 (MyD88) as an adapter to recruit the signaling pathways leading to the activation of the transcription factors NF-kB, and in some cases interferon regulatory factor (IRF) 7, resulting in the production of pro-inflammatory cytokines and type I IFN. TLR3, on the other hand, utilizes the TIR domain-containing adaptor protein inducing interferon β (TRIF) to activate nuclear factor kappa-light-chain-enhancer of activated B cells…