Immunoregulation of antigen presenting and secretory functions of monocytic cells by Helicobacter pylori antigens in relation to impairment of lymphocyte expansion

Abstract

The role of Helicobacter pylori (H. pylori) antigens in driving a specific immune response against the bacteria causing gastroduodenal disorders is poorly understood. Using a guinea pig model mimicking the natural history of H. pylori infection, we evaluated the effectiveness of immature and mature macrophages in promoting the blastogenesis of splenocytes from H. pylori infected and uninfected animals, in response to H. pylori antigens: glycine acid extract (GE), cytotoxin associated gene A protein (CagA), urease A (UreA) and lipopolysaccharide (LPS). Lymphocyte expansion was assessed in 72 h cell cultures, containing: immature or mature macrophages derived from bone marrow monocytes, unstimulated or stimulated with H. pylori antigens for 2 h. The proliferation was expressed as a ratio of [(3)H]-thymidine incorporation into DNA of antigen-stimulated to unstimulated cells and the DNA damage was determined by DAPI cell staining. TGF-β and IFN-γ were assessed immunoenzymatically in cell culture supernatants. Lymphocytes of control and H. pylori-infected animals proliferated intensively in response to phytohaemagglutinin (PHA) and in co-cultures with immature or mature macrophages treated with CagA or UreA (significantly) and GE (slightly) exluding the cultures containing H. pylori or E. coli LPS. This lymphocyte growth inhibition was related to DNA damage of monocytic cells in response to H. pylori or E. coli LPS and secretion of regulatory TGF-β, but not proinflammatory IFN-γ. Impaired homeostasis of monocytic cell function related to DNA damage and TGF-β release, in response to H. pylori LPS may lead to the suppression of adaptive immune response against the bacteria and development of chronic infection.

Impact ofHelicobacter pylorion the healing process of the gastric barrier

“…H. pylori antigens penetrating across the gastric epithelium, can be processed in lamina propria by macrophages via PRR and presented to T lymphocytes[8,19,20]. However, it has been shown that H. pylori LPS is able to downregulate the lymphocyte blastogenic response, probably due to the interference with the process of macrophage maturation[46-48,94]. It also downregulates the phagocytic potential of macrophages[44] and decreases the cytotoxic activity of NK cells[45,68].…”

“…The antigen concentrations were adjusted experimentally or adopted from previously performed experiments[44,47,48,68]. …”

“…This is by reducing the host immune response mechanisms including phagocytosis[44], Natural Killer cells activity[45] and proliferation of T lymphocytes[46-48]. LPS through binding with dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) may interfere with the development of specific immune response[49,50].…”

Host pathogen interactions in Helicobacter pylori related gastric cancer

“…The ability to glycosylate host cholesterol is crucial for the virulence and antibiotic resistance of H. pylori [12]. H. pylori lipopolysaccharide (LPS), due to its structural features, induces a poor immune response and helps the bacteria develop into a chronic infection[13-18]. H. pylori LPS may carry various human Lewis (Le)-like antigens, which may play a role in autoimmunity.…”

“…The primary host immune response mechanisms, such as phagocytosis and natural killer (NK) cell activity, have been found to be downregulated by H. pylori LPS[17,18,39,40]. Adaptive immunity is also targeted by H. pylori compounds[1,15,41,42].…”