The CagA protein of Helicobacter pylori suppresses the functions of dendritic cell in mice.
CagA protein is the most assessed effecter molecule of Helicobacter pylori. In this report, we demonstrate how CagA protein regulates the functions of dendritic cells (DC) against H. pylori infection. In addition, we found that CagA protein was tyrosine-phosphorylated in DC. The responses to cagA-positive H. pylori in DC were reduced in comparison to those induced by cagA-negative H. pylori. CagA-overexpressing DC also exhibited a decline in the responses against LPS stimulation and the differentiation of CD4(+) T cells toward Th1 type cells compared to wild type DC. In addition, the level of phosphorylated IRF3 decreased in CagA-overexpressing DC stimulated with LPS, indicating that activated SHP-2 suppressed the enzymatic activity of TBK1 and consequently IRF3 phosphorylation. These data suggest that CagA protein negatively regulates the functions of DC via CagA phosphorylation and that cagA-positive H. pylori strains suppress host immune responses resulting in their chronic colonization of the stomach.
Tanaka
Hiroshi
H
Department of Internal Medicine, Kobe University, Chu-o-ku, Hyogo, Japan.
Yoshida
Masaru
M
Nishiumi
Shin
S
Ohnishi
Naomi
N
Kobayashi
Kazuki
K
Yamamoto
Koji
K
Fujita
Tsuyoshi
T
Hatakeyama
Masanori
M
Azuma
Takeshi
T
D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000502:physiology*; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010766:Phosphorylation / Q000276:immunology; D013270:Stomach / Q000382:microbiology / Q000473:pathology; D013274:Stomach Neoplasms / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D014443:Tyrosine / Q000378:metabolism
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D007166:Immunosuppressive Agents; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; C080866:cagA protein, Helicobacter pylori; D014443:Tyrosine