Partial protection against Helicobacter pylori in the absence of mast cells in mice.
The goal of this study is to evaluate the contribution of mast cells to Helicobacter pylori immunity in a model of vaccine-induced protection. Mast cell-deficient Kitl(Sl)/Kitl(Sl-d) and control mice were immunized with H. pylori sonicate plus cholera toxin and challenged with H. pylori, and the bacterial loads, inflammatory infiltrates, and cytokine responses were evaluated and compared at 1, 2, and 4 weeks postchallenge. In vitro stimulation assays were performed using bone marrow-derived mast cells, and recall assays were performed with spleen cells of immunized mast cell-deficient and wild-type mice. Bacterial clearance was observed by 2 weeks postchallenge in mast cell-deficient mice. The bacterial load was reduced by 4.0 log CFU in wild-type mice and by 1.5 log CFU in mast cell-deficient mice. Neutrophil numbers in the gastric mucosa of immune Kitl(Sl)/Kitl(Sl-d) mice were lower than those for immune wild-type mice (P < 0.05). Levels of gastric interleukin-17 (IL-17) and tumor necrosis factor alpha (TNF-alpha) were also significantly lower in immune Kitl(Sl)/Kitl(Sl-d) mice than in wild-type mice (P < 0.001). Immunized mast cell-deficient and wild-type mouse spleen cells produced IFN-gamma and IL-17 in response to H. pylori antigen stimulation. TNF-alpha and CXC chemokines were detected in mast cell supernatants after 24 h of stimulation with H. pylori antigen. The results indicate that mast cells are not essential for but do contribute to vaccine-induced immunity and that mast cells contribute to neutrophil recruitment and inflammation in response to H. pylori.
Ding
Hua
H
Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Nedrud
John G
JG
Wershil
Barry
B
Redline
Raymond W
RW
Blanchard
Thomas G
TG
Czinn
Steven J
SJ
D000818:Animals; D054360:Chemokine CXCL1 / Q000032:analysis; D054426:Chemokine CXCL2 / Q000032:analysis; D015169:Colony Count, Microbial; D005753:Gastric Mucosa / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D016481:Helicobacter Infections / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D016480:Helicobacter pylori / Q000276:immunology*; D020381:Interleukin-17 / Q000032:analysis; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology; D013270:Stomach / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha