Chronic
inflammation has been associated with an increased risk of several human
malignancies, a classic example being gastric
adenocarcinoma (GC). Development of GC is known to result from
infection of the gastric mucosa by Helicobacter pylori, which initially induces acute
inflammation and, in a subset of patients, progresses over time to chronic
inflammation, gastric
atrophy, intestinal
metaplasia, dysplasia, and finally intestinal-type GC. Germ-line encoded receptors known as
pattern-recognition receptors (
PRRs) are critical for generating mature pro-inflammatory
cytokines that are crucial for both Th1 and Th2 responses. Given that H. pylori is initially targeted by
PRRs, it is conceivable that dysfunction within genes of this arm of the immune system could modulate the host response against H. pylori
infection, and subsequently influence the emergence of GC. Current evidence suggests that
Toll-like receptors (TLRs) (TLR2, TLR3, TLR4, TLR5, and TLR9),
nucleotide-binding oligomerization domain (
NOD)-like receptors (NLRs) (NOD1, NOD2, and NLRP3), a
C-type lectin receptor (
DC-SIGN), and
retinoic acid-inducible gene (RIG)-I-like receptors (RIG-I and MDA-5), are involved in both the recognition of H. pylori and gastric
carcinogenesis. In addition, polymorphisms in genes involved in the TLR (TLR1, TLR2, TLR4, TLR5, TLR9, and CD14) and NLR (NOD1, NOD2, NLRP3, NLRP12, NLRX1, CASP1, ASC, and CARD8) signaling pathways have been shown to modulate the risk of H. pylori
infection, gastric precancerous lesions, and/or GC. Further, the modulation of
PRRs has been suggested to suppress H. pylori-induced
inflammation and enhance GC cell apoptosis, highlighting their potential relevance in GC
therapeutics. In this review, we present current advances in our understanding of the role of the TLR and NLR signaling pathways in the pathogenesis of GC, address the involvement of other recently identified
PRRs in GC, and discuss the potential implications of
PRRs in GC
immunotherapy.