Bacterial chemotaxis modulates host cell apoptosis to establish a T-helper cell, type 17 (Th17)-dominant immune response in Helicobacter pylori infection

Proc Natl Acad Sci U S A. 2011 Dec 6;108(49):19749-54. doi: 10.1073/pnas.1104598108. Epub 2011 Nov 21.

Abstract

The host inflammatory response to chronic bacterial infections often dictates the disease outcome. In the case of the gastric pathogen Helicobacter pylori, host inflammatory responses result in outcomes that range from moderate and asymptomatic to more severe with concomitant ulcer or cancers. It was found recently that H. pylori chemotaxis mutants (Che(-)), which lack directed motility but colonize to nearly wild-type levels, trigger less host inflammation. We used these mutants to observe host immune responses that resulted in reduced disease states. Here we report that these mutants are defective for early gastric recruitment of CD4(+) T cells compared with wild-type infection. Furthermore, Che(-) mutant infections lack the T-helper cell, type 17 (Th17) component of the immune response, as measured by cytokine mRNA levels in gastric tissue via intracellular cytokine staining and immunofluorescence. We additionally find that a Che(-) mutant infection results in significantly less host cell apoptosis than does wild-type infection, in accordance with previous observations that T-helper cell, type 17 responses in Citrobacter rodentium infections are driven by concomitant bacterial and apoptotic cell signals. We propose that bacterial chemotaxis allows H. pylori to access a particular host niche that allows the bacteria to express or deliver proapoptotic host cell factors. This report indicates that chemotaxis plays a role in enhancing apoptosis, suggesting bacterial chemotaxis systems might serve as therapeutic targets for infections whose symptoms arise from host cell apoptosis and tissue damage.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Bacterial Physiological Phenomena / genetics
  • Bacterial Proteins / genetics
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Citrobacter rodentium / immunology
  • Citrobacter rodentium / physiology
  • Coinfection
  • Cytokines / genetics
  • Cytokines / metabolism
  • Enterobacteriaceae Infections / immunology
  • Enterobacteriaceae Infections / metabolism
  • Enterobacteriaceae Infections / microbiology
  • Female
  • Flow Cytometry
  • Gastric Mucosa / immunology
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / microbiology
  • Gastritis / immunology
  • Gastritis / metabolism
  • Gastritis / microbiology
  • Helicobacter Infections / immunology
  • Helicobacter Infections / metabolism
  • Helicobacter Infections / microbiology*
  • Helicobacter pylori / genetics
  • Helicobacter pylori / immunology
  • Helicobacter pylori / physiology*
  • Host-Pathogen Interactions
  • Immunohistochemistry
  • Locomotion / genetics
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Methyl-Accepting Chemotaxis Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Reverse Transcriptase Polymerase Chain Reaction
  • Th17 Cells / immunology
  • Th17 Cells / metabolism*

Substances

  • Bacterial Proteins
  • Cytokines
  • Membrane Proteins
  • Methyl-Accepting Chemotaxis Proteins