Helicobacter pylori-secreted factors inhibit dendritic cell IL-12 secretion: a mechanism of ineffective host defense.
Helicobacter pylori evades host immune defenses and causes chronic gastritis. Immunity against intestinal pathogens is largely mediated by dendritic cells, yet the role of dendritic cells in acute H. pylori infection is largely unknown. We observed the recruitment of dendritic cells to the gastric mucosa of H. pylori-infected mice. Bone marrow-derived dendritic cells from mice responded to live H. pylori by upregulating the expression of proinflammatory cytokine mRNA (i.e., IL-1alpha, IL-1beta, and IL-6). The supernatant from dendritic cells stimulated with H. pylori for 18 h contained twofold higher levels of IL-12p70 than IL-10 and induced the proliferation of syngeneic splenocytes and type 1 T helper cell cytokine release (IFN-gamma and TNF-alpha). These responses were significantly lower compared with those induced by Acinetobacter lwoffi, another gastritis-causing pathogen more susceptible to host defenses. Analysis of whole H. pylori sonicate revealed the presence of a heat-stable factor secreted from H. pylori that specifically inhibited IL-12 but not IL-10 release from dendritic cells activated by A. lwoffi. Our findings suggest that dendritic cells participate in the host immune response against H. pylori and that their suppression by H. pylori may explain why infected hosts fail to prevent bacterial colonization.
Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI 48109-0682, USA. jykao@umich.edu
John Y
JY
Kao
Sivaprakash
S
Rathinavelu
Kathryn A
KA
Eaton
Longchuan
L
Bai
Yana
Y
Zavros
Mimi
M
Takami
Anna
A
Pierzchala
Juanita L
JL
Merchant
D000150:Acinetobacter / Q000276:immunology; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology*; D005753:Gastric Mucosa / Q000276:immunology* / Q000382:microbiology*; D016480:Helicobacter pylori / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL
D001426:Bacterial Proteins; D016207:Cytokines; D018664:Interleukin-12