Regulation of cellular immunity prevents Helicobacter pylori-induced atherosclerosis.
Helicobacter pylori (H. pylori) is a predominant pathogen that causes not only gastroduodenal diseases but also extra-alimentary tract diseases. In this study, we demonstrated that H. pylori infection promoted atherogenesis in heterozygous apoe(+/ --) ldlr(+/--) mice. The male mice were fed with high fat diet from the age of 6 weeks. At the age of 16 weeks, development of atherosclerotic lesions was observed in the H. pylori-infected mice, and it seemed to be associated with an elevation of Th1-immune response against H. pylori origin-heat shock protein 60 (Hp-HSP60) and an increment of transendothelial migration of T cells. Subcutaneous immunisation with Hp-HSP60 or H. pylori eradication with antibiotics significantly reduced the progression of atherosclerosis, accompanied by a decline of Th1 differentiation and reduction of their chemotaxis beyond the endothelium. Thus, oral infection with H. pylori accelerates atherosclerosis in mice and the active immunisation with Hp-HSP60 or the eradication of H. pylori with antibiotics can moderate/prevent cellular immunity, resulting in a reduction of atherosclerosis.
Ayada
K
K
Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Yokota
K
K
Hirai
K
K
Fujimoto
K
K
Kobayashi
K
K
Ogawa
H
H
Hatanaka
K
K
Hirohata
S
S
Yoshino
T
T
Shoenfeld
Y
Y
Matsuura
E
E
Oguma
K
K
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000209:etiology* / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D002465:Cell Movement / Q000502:physiology; D018834:Chaperonin 60 / Q000235:genetics / Q000276:immunology; D018925:Chemokines / Q000276:immunology; D004041:Dietary Fats; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D016481:Helicobacter Infections / Q000150:complications / Q000276:immunology; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology
D001057:Apolipoproteins E; D018834:Chaperonin 60; D018925:Chemokines; C515188:Cxcr3 protein, mouse; D004041:Dietary Fats; D054367:Receptors, CXCR3; D011973:Receptors, LDL