Search

Intracellular bacterial pathogens have developed versatile strategies to generate niches inside the eukaryotic cells that allow them to survive and proliferate. Making a home inside the host offers many advantages; however, intracellular bacteria must also overcome many challenges, such as disarming innate immune signaling and accessing host nutrient supplies. Gaining entry into the cell and avoiding degradation is only the beginning of a successful intracellular lifestyle. To establish these replicative niches, intracellular pathogens secrete various virulence proteins, called effectors, to manipulate host cell signaling pathways and subvert host defense mechanisms. Many effectors mimic host enzymes, whereas others perform entirely novel enzymatic functions. A large volume of work has been done to understand how intracellular bacteria manipulate membrane trafficking pathways. In this review, we focus on how intracellular bacterial pathogens target innate immune signaling, the unfolded protein response, autophagy, and cellular metabolism and exploit these pathways to their advantage. We also discuss how bacterial pathogens can alter host gene expression by directly modifying histones or hijacking the ubiquitination machinery to take control of several host signaling pathways.

Aim: To evaluate the frequency of Helicobacter pylori ( H. pylori ) CagA antibodies in H. pylori infected subjects and to identify potential histopathological and bacterial factors related to H. pylori CagA-immune response., Methods: Systematic data to H. pylori isolates, blood samples, gastric biopsies for histological and molecular analyses were available from 99 prospectively recruited subjects. Serological profile (anti- H. pylori , anti-CagA) was correlated with H. pylori isolates ( cagA , EPIYA, vacA s/m genotype), histology (Sydney classification) and mucosal interleukin-8 (IL-8) mRNA and protein expression. Selected H. pylori strains were assessed for H. pylori CagA protein expression and IL-8 induction in co-cultivation model with AGS cells., Results: Thirty point three percent of microbiologically confirmed H. pylori infected patients were seropositive for CagA. Majority of H. pylori isolates were cagA gene positive (93.9%) with following vacA polymorphisms: 42.4% vacA s1m1 , 23.2% s1m2 and 34.3% s2m2 . Anti-CagA-IgG seropositivity was strongly associated with atrophic gastritis, increased mucosal inflammation according to the Sydney score, IL-8 and cagA mRNA expression. VacA s and m polymorphisms were the major determinants for positive ( vacA s1m1) or negative ( vacA s2m2) anti-CagA serological immune response, which also correlated with the in vitro inflammatory potential in AGS cells. In vitro co-cultivation of representative H. pylori strains with AGS cells confirmed functional CagA translocation, which showed only partial correlation with CagA seropositivity in patients, supporting vacA as major co-determinant of the immune response., Conclusion: Serological immune response to H. pylori cagA + strain in H. pylori infected patients is strongly associated with vacA polymorphism, suggesting the crucial role of bacterial factors in immune and clinical phenotype of the infection., Competing Interests: Conflict-of-interest statement: The authors have no conflicts to declare.