Abstract
Toll-like receptors (TLR) are essential for Helicobacter pylori (Hp) recognition and subsequent innate and adaptive immunity responses. TLR2 appears to be the receptor responsible for most of the immunologic reaction against Hp infection. However, TLR4, TLR9 and eventually TLR5 may also have a synergic effect with TLR2 against Hp. It has been shown that gastric Hp infection increases TLR expression in the gastric mucosa. Moreover, recent studies have shown that human gastric carcinogenesis is associated not only with increased expression of TLR but also with decreased expression of their inhibitors such as Toll-Interacting Protein (TOLLIP) and peroxisome proliferator-activated receptor (PPAR)-g. Indeed, gastric dysplasia and adenocarcinoma are associated with high expression levels of TLR and low levels of TOLLIP and PPAR-g, suggesting increased activation of these receptors throughout human gastric carcinogenesis. In this article we discuss how these novels findings could be used not only for the diagnosis and prognosis of gastric lesions associated with Hp infection but also for their treatment. Specifically, we discuss the potential use of TLR agonists in addition to antibiotics to improve eradication rates of Hp and of TLR antagonists to slow the progression of gastric preneoplastic lesions. We also discuss the potential value of TLR signalling blockers and quantification of tumoral TLR expression, respectively, in the treatment and prognosis of gastric cancer. In conclusion, TLRs can be an important link between Hp and the sequence of gastric carcinogenesis and they can be used as biomarkers of gastric carcinogenesis. In this article, future lines of investigation related with these novel scientific findings are proposed and discussed.
Highlights
Gastric pathology has some unique characteristics mainly because many gastric diseases have a strong association with a bacteria infection—Helicobacter pylori (Hp)
Toll-like receptors (TLR) can be an important link between Hp and the sequence of gastric carcinogenesis and they can be used as biomarkers of gastric carcinogenesis
As we have seen progression of gastric lesions is associated with increasing levels of TLRs and diminished TLRs inhibitors
Summary
Gastric pathology has some unique characteristics mainly because many gastric diseases have a strong association with a bacteria infection—Helicobacter pylori (Hp). The innate immune system is the first line of defense against several microbial agents, consisting of a diversity of components that initiate protective immunological responses [13,14] Many of these factors can prevent or destroy the invading pathogens non-we know that the microbiological recognition by innate immunity is a specific and highly coordinated process involving pattern recognition receptors (PRRs) that identify preserved structures of different pathogens, the so-called pathogen-associated molecular patterns (PAMPs) [13,14]. Despite similar intracellular signalling pathways, the final result of stimulating different TLRs is not exactly the same depending of the activated receptor and of the cell that is stimulated [30,31,32] Because they are intrinsically related to inflammation and to cell survival signalling, epithelial regeneration and cell proliferation, recent reports associate these receptors function to tumorigenesis [33,34]. In this article we will discuss the fundamental role of TLRs in the immunological response to HP infection and in the progression of gastric preneoplastic lesions and how this novel finding could potentially be used in clinical practice
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