Submitted on March 28, 2005
Accepted on February 1, 2006
Helicobacter pylori-secreted factors inhibit dendritic cell IL-12 secretion: a mechanism of ineffective host defense
John Y. Kao1*, Sivaprakash Rathinavelu1, Kathryn A. Eaton2, Longchuan Bai1, Yana Zavros1, Mimi Takami1, Anna Pierzchala1, and Juanita L. Merchant1
1 Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
2 Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA
* To whom correspondence should be addressed. E-mail: jykao{at}umich.edu.
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 up-regulating the expression of pro-inflammatory cytokine mRNA (i.e., IL-1
, IL-1
, and IL-6). The supernatant from dendritic cells stimulated with H. pylori for 18 h contained 2-fold higher levels of IL-12p70 than IL-10 and induced proliferation of syngeneic splenocytes and Th1 cytokine release (IFN-
and TNF-). These responses were significantly lower in comparison to 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 inhibits 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.
