Genetic Variability as a Regulator of TLR4 and NOD Signaling in Response to Bacterial Driven DNA Damage Response (DDR) and Inflammation: Focus on the Gastrointestinal (GI) Tract

Evagelia Spanou; Polyxeni Kalisperati; Ioannis S Pateras; Alexandros Papalampros; Alexandra Barbouti; Athanasios G Tzioufas; Athanassios Kotsinas; Stavros Sougioultzis

doi:10.3389/fgene.2017.00065

Genetic Variability as a Regulator of TLR4 and NOD Signaling in Response to Bacterial Driven DNA Damage Response (DDR) and Inflammation: Focus on the Gastrointestinal (GI) Tract

Front Genet. 2017 May 29:8:65. doi: 10.3389/fgene.2017.00065. eCollection 2017.

Authors

Evagelia Spanou¹, Polyxeni Kalisperati¹, Ioannis S Pateras², Alexandros Papalampros³, Alexandra Barbouti⁴, Athanasios G Tzioufas⁵, Athanassios Kotsinas², Stavros Sougioultzis¹

Affiliations

¹ Gastroenterology Division, Department of Pathophysiology, "Laikon" General Hospital, University of AthensAthens, Greece.
² Department of Histology and Embryology, University of AthensAthens, Greece.
³ 1st Department of Surgery, "Laikon" General Hospital, University of AthensAthens, Greece.
⁴ Department of Anatomy-Histology-Embryology, University of IoanninaIoannina, Greece.
⁵ Department of Pathophysiology, "Laikon" General Hospital, University of AthensAthens, Greece.

Abstract

The fundamental role of human Toll-like receptors (TLRs) and NOD-like receptors (NLRs), the two most studied pathogen recognition receptors (PRRs), is the protection against pathogens and excessive tissue injury. Recent evidence supports the association between TLR/NLR gene mutations and susceptibility to inflammatory, autoimmune, and malignant diseases. PRRs also interfere with several cellular processes, such as cell growth, apoptosis, cell proliferation, differentiation, autophagy, angiogenesis, cell motility and migration, and DNA repair mechanisms. We briefly review the impact of TLR4 and NOD1/NOD2 and their genetic variability in the process of inflammation, tumorigenesis and DNA repair, focusing in the gastrointestinal tract. We also review the available data on new therapeutic strategies utilizing TLR/NLR agonists and antagonists for cancer, allergic diseases, viral infections and vaccine development against both infectious diseases and cancer.

Keywords: DNA damage response (DDR); inflammation and tumorigenesis; mutation; nod-like receptors (NLRs); single nucleotide polymorphism (SNP); toll-like receptors (TLRs).

Publication types

Review