Helicobacter pylori arginase inhibits T cell proliferation and reduces the expression of the TCR zeta-chain (CD3zeta).
Helicobacter pylori infects approximately half the human population. The outcomes of the infection range from gastritis to gastric cancer and appear to be associated with the immunity to H. pylori. Patients developing nonatrophic gastritis present a Th1 response without developing protective immunity, suggesting that this bacterium may have mechanisms to evade the immune response of the host. Several H. pylori proteins can impair macrophage and T cell function in vitro through mechanisms that are poorly understood. We tested the effect of H. pylori extracts and live H. pylori on Jurkat cells and freshly isolated human normal T lymphocytes to identify possible mechanisms by which the bacteria might impair T cell function. Jurkat cells or activated T lymphocytes cultured with an H. pylori sonicate had a reduced proliferation that was not caused by T cell apoptosis or impairment in the early T cell signaling events. Instead, both the H. pylori sonicate and live H. pylori induced a decreased expression of the CD3zeta-chain of the TCR. Coculture of live H. pylori with T cells demonstrated that the wild-type strain, but not the arginase mutant rocF(-), depleted L-arginine and caused a decrease in CD3zeta expression. Furthermore, arginase inhibitors reversed these events. These results suggest that H. pylori arginase is not only important for urea production, but may also impair T cell function during infection.
Zabaleta
Jovanny
J
Department of Pathology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
McGee
David J
DJ
Zea
Arnold H
AH
Hernández
Claudia P
CP
Rodriguez
Paulo C
PC
Sierra
Rosa A
RA
Correa
Pelayo
P
Ochoa
Augusto C
AC
D017209:Apoptosis; D001119:Arginase / Q000502:physiology*; D018920:Coculture Techniques; D016481:Helicobacter Infections / Q000276:immunology; D016480:Helicobacter pylori / Q000201:enzymology* / Q000472:pathogenicity; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000032:analysis*; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain; D001119:Arginase