The Helicobacter pylori Autotransporter ImaA (HP0289) Modulates the Immune Response and Contributes to Host Colonization
Open Access
- 1 July 2012
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 80 (7), 2286-2296
- https://doi.org/10.1128/iai.00312-12
Abstract
The human pathogen Helicobacter pylori employs a diverse collection of outer membrane proteins to colonize, persist, and drive disease within the acidic gastric environment. In this study, we sought to elucidate the function of the host-induced gene HP0289 , which encodes an uncharacterized outer membrane protein. We first generated an isogenic H. pylori mutant that lacks HP0289 and found that the mutant has a colonization defect in single-strain infections and is greatly outcompeted in mouse coinfection experiments with wild-type H. pylori . Furthermore, we used protease assays and biochemical fractionation coupled with an HP0289-targeted peptide antibody to verify that the HP0289 protein resides in the outer membrane. Our previous findings showed that the HP0289 promoter is upregulated in the mouse stomach, and here we demonstrate that HP0289 expression is induced under acidic conditions in an ArsRS-dependent manner. Finally, we have shown that the HP0289 mutant induces greater expression of the chemokine interleukin-8 (IL-8) and the cytokine tumor necrosis factor alpha (TNF-α) in gastric carcinoma cells (AGS). Similarly, transcription of the IL-8 homolog keratinocyte-derived chemokine (KC) is elevated in murine infections with the HP0289 mutant than in murine infections with wild-type H. pylori . On the basis of this phenotype, we renamed HP0289 ImaA for i mmuno m odulatory a utotransporter protein. Our work has revealed that genes induced in vivo play an important role in H. pylori pathogenesis. Specifically, the outer membrane protein ImaA modulates a component of the host inflammatory response, and thus may allow H. pylori to fine tune the host immune response based on ImaA expression.Keywords
This publication has 84 references indexed in Scilit:
- BabA-mediated Adherence Is a Potentiator of the Helicobacter pylori Type IV Secretion System ActivityJournal of Biological Chemistry, 2011
- The Pfam protein families databaseNucleic Acids Research, 2009
- Helicobacter pylori CagA activates NF‐κB by targeting TAK1 for TRAF6‐mediated Lys 63 ubiquitinationEMBO Reports, 2009
- Recombination-Based In Vivo Expression Technology IdentifiesHelicobacter pyloriGenes Important for Host ColonizationInfection and Immunity, 2008
- Serendipitous Discovery of an Immunoglobulin-Binding Autotransporter in Bordetella SpeciesInfection and Immunity, 2008
- Helicobacter exploits integrin for type IV secretion and kinase activationNature, 2007
- Helicobacter pyloriChemotaxis Modulates Inflammation and Bacterium-Gastric Epithelium Interactions in Infected MiceInfection and Immunity, 2007
- Cleavage of a bacterial autotransporter by an evolutionarily convergent autocatalytic mechanismThe EMBO Journal, 2007
- Role of Transcription Factor T-bet Expression by CD4+Cells in Gastritis Due toHelicobacter pyloriin MiceInfection and Immunity, 2006
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001