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.
Wang
Ya-Hui
YH
Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan, Republic of China.
Gorvel
Jean-Pierre
JP
Chu
Yen-Ting
YT
Wu
Jiunn-Jong
JJ
Lei
Huan-Yao
HY
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