Helicobacter pylori impairs murine dendritic cell responses to infection.
BACKGROUND
Helicobacter pylori, a human pathogen associated with chronic gastritis, peptic ulcer and gastric malignancies, is generally viewed as an extracellular microorganism. Here, we show that H. pylori replicates in murine bone marrow derived-dendritic cells (BMDCs) within autophagosomes.


RESULTS
A 10-fold increase of CFU is found between 2 h and 6 h p.i. in H. pylori-infected BMDCs. Autophagy is induced around the bacterium and participates at late time points of infection for the clearance of intracellular H. pylori. As a consequence of infection, LC3, LAMP1 and MHC class II molecules are retained within the H. pylori-containing vacuoles and export of MHC class II molecules to cell surface is blocked. However, formalin-fixed H. pylori still maintain this inhibitory activity in BMDC derived from wild type mice, but not in from either TLR4 or TLR2-deficient mice, suggesting the involvement of H. pylori-LPS in this process. TNF-alpha, IL-6 and IL-10 expression was also modulated upon infection showing a TLR2-specific dependent IL-10 secretion. No IL-12 was detected favoring the hypothesis of a down modulation of DC functions during H. pylori infection. Furthermore, antigen-specific T cells proliferation was also impaired upon infection.


CONCLUSIONS
H. pylori can infect and replicate in BMDCs and thereby affects DC-mediated immune responses. The implication of this new finding is discussed for the biological life cycle of H. pylori in the host.
Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan, Republic of China.
Ya-Hui
YH
Wang
Jean-Pierre
JP
Gorvel
Yen-Ting
YT
Chu
Jiunn-Jong
JJ
Wu
Huan-Yao
HY
Lei
D000818:Animals; D001343:Autophagy; D001692:Biological Transport; D001854:Bone Marrow Cells / Q000166:cytology; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology* / Q000648:ultrastructure; D005260:Female; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology*; D016480:Helicobacter pylori / Q000166:cytology / Q000276:immunology* / Q000648:ultrastructure; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4