MOLECULAR MECHANISM OF INNATE IMMUNE RESPONSE ACTIVATION BY HELICOBACTER PYLORI

Helicobacter pylori (H. pylori) bacteria are first recognized by natural immune system following their interaction with pattern recognition receptors (PRRs) which are present on immune cells and epithelial cells of the stomach. The PPRs consist of at least four receptor groups: Toll-like receptors (TLRs), NOD like receptors (NLRs), RIG like receptors (RLRs) and C-type lectin receptors (CLRs). These receptors are evolutionarily conserved. The PPRs are critical to watching specific immune mechanisms in response to infectious and non-infectious factors. These receptors recognize specific microbial specificity (ligands), such as lipopolysacchafide (TLR-4), lipoprotein (TLR-2), flagellin (TLR-5) and unmethylated CpG DNA regions (TLR-9). They have an extracellular (TLR-2, TLR- 4, TLR-5, CLR (DC-SIGN)), cytoplasmic (NLRs), endosomal (TLR-9, RLRs) location. After binding the appropriate bacterial ligands, all of these receptors trigger cell signaling pathways to initiate synthesis of inflammatory mediators. This mechanism creates a profile of immune response, which may result in elimination of the infectious agent (protective effects), or lack of elimination (chronic inflammation). This mechanism is strictly controlled by negative regulatory proteins and microRNAs. H. pylori has the ability to manipulate the immune system of the host in a way that it does not react to H. pylori ligands (especially LPS). As a result endotoxin tolerance is induced. This prevents H. pylori elimination and allows the bacterium to survive in the gastric mucosa. Interaction H. pylori and host immune system, impact on chronic inflammation and ultimately, can lead to atrophy of the gastric mucosa, and consequently gastric cancer.