Helicobacter pylori inhibits phagocytosis by professional phagocytes involving type IV secretion components

Abstract

Gastric infections by Helicobacter pylori are characteristically associated with an intense inflammation and infiltration of mainly polymorphonuclear lymphocytes (PMNs) and monocytes. The inflammatory response by infiltrated immune cells appears to be a primary cause of the damage to surface epithelial layers and may eventually result in gastritis, peptic ulcer, gastric cancer and/or MALT‐associated gastric lymphoma. Our analysis of the interaction between H. pylori and PMNs and monocytes revealed that H. pylori inhibits its own uptake by these professional phagocytes. To some degree, this effect resembles antiphagocytosis by Yersinia enterocolitica. Increasing numbers of bacteria associated per cell are more efficient at blocking their own engulfment. In H. pylori, bacterial protein synthesis is necessary to block phagocytic uptake, as shown by the time and concentration dependence of the bacteriostatic protein synthesis inhibitor chloramphenicol. Furthermore, H. pylori appears broadly to inhibit the phagocytic function of monocytes and PMNs, as infection with H. pylori abrogates the phagocytes' ability to engulf latex beads or adherent Neisseria gonorrhoeae cells. This antiphagocytic phenotype depends on distinct virulence (vir) genes, such as virB7 and virB11, encoding core components of a putative type IV secretion apparatus. Our data indicate that H. pylori exhibits an antiphagocytic activity that may play an essential role in the immune escape of this persistent pathogen.

Conjugal type IV macromolecular transfer systems of Gram-negative bacteria: organismal distribution, structural constraints and evolutionary conclusions

“…Other systems such as the Tra system of plasmid IncF (cluster 9) seem to lack several constituents, possibly because of incomplete plasmid sequencing. The VirB8, B9 and B10 proteins, and possibly VirB11 as well, that comprise cluster 2 probably form a structure that functions in a unified capacity, possibly in virulence and\or competence in H. pylori (Ramarao et al, 2000) and Ric. prowazekii by a mechanism that does not utilize a complete IVSP system.…”

“…The VirB7 family consists of 11 proteins, all of about 55 residues. An additional potential VirB7 homologue was reported by Ramarao et al (2000), but it differs in size from other VirB7 homologues and shows insufficient sequence similarity to establish homology. Therefore, this protein was omitted from our studies.…”

“…Ten proteins have been directly implicated in the DNA transfer process (Berger & Christie, 1994 ;Burns, 1999 ;Christie, 1997 ;de la Cruz & Lanka, 1998 ;Kuldau et al, 1990 ;Thorstenson et al, 1993 ;Winans et al, 1996). A related export system mediates pertussis toxin secretion (Covacci & Rappuoli, 1993 ;Nicosia et al, 1986 ;Weiss et al, 1993) and the H. pylori and Legionella pneumophila genomes encode genes related to IVSP system constituents that are important for virulence (Covacci et al, 1997(Covacci et al, , 1999Ramarao et al, 2000 ;Segal et al, 1998 ;Tummuru et al, 1995 ;Vogel et al, 1998). The agrobacterial system has recently been shown to translocate free proteins as well as nucleoprotein complexes (Vergunst et al, 2000).…”

Impact of Helicobacter pylori Virulence Factors and Compounds on Activation and Maturation of Human Dendritic Cells

“…Recently, H. pylori arginase was reported to inhibit T-cell proliferation by reducing the expression of the TCR -chain (66). In addition, cag-PAI-positive H. pylori strains inhibit phagocytosis by macrophages (2,3,49), and VacA interferes with the Ii-dependent pathway of antigen presentation (44).…”

Helicobacter pylori Arginase Inhibits T Cell Proliferation and Reduces the Expression of the TCR ζ-Chain (CD3ζ)

“…Therefore, it is possible that H. pylori, like other bacteria, has mechanisms to escape the immune response. Virulent strains of H. pylori carrying the cag pathogenicity island (PAI) 3 delay phagocytosis by macrophages in vitro and are killed less efficiently than those without the PAI element (21)(22)(23). Recent reports have also shown that cytotoxinassociated protein A (CagA) binds to Src homology protein tyrosine phosphatase 2, which could impair signal transduction in cells (24).…”