TY - JOUR
T1 - Helicobacter pylori-secreted factors inhibit dendritic cell IL-12 secretion
T2 - A mechanism of ineffective host defense
AU - Kao, John Y.
AU - Rathinavelu, Sivaprakash
AU - Eaton, Kathryn A.
AU - Bai, Longchuan
AU - Zavros, Yana
AU - Takami, Mimi
AU - Pierzchala, Anna
AU - Merchant, Juanita L.
PY - 2006
Y1 - 2006
N2 - 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-1α, IL-1β, 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-γ and TNF-α). 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.
AB - 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-1α, IL-1β, 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-γ and TNF-α). 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.
KW - Acinetobacter lwoffi
KW - Antigen-presenting cells
KW - Inflammation
KW - Interferon-γ
KW - Interleukin-10
UR - http://www.scopus.com/inward/record.url?scp=33745804730&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33745804730&partnerID=8YFLogxK
U2 - 10.1152/ajpgi.00139.2005
DO - 10.1152/ajpgi.00139.2005
M3 - Article
C2 - 16469828
SN - 0193-1857
VL - 291
SP - G73-G81
JO - American Journal of Physiology - Gastrointestinal and Liver Physiology
JF - American Journal of Physiology - Gastrointestinal and Liver Physiology
IS - 1
ER -