Impaired dendritic cell functions disrupt antigen-specific adaptive immune responses in mice with nonalcoholic fatty liver disease.
OBJECTIVE
The magnitude of antigen-specific immunity was assessed in a murine model of nonalcoholic fatty liver diseases (NAFLD). Because antigen-specific immunity was diminished in NAFLD mice, the underlying mechanisms were evaluated through analysis of the functions of antigen-presenting dendritic cells (DC) and other immunocytes.


METHODS
For 12 weeks, NAFLD mice received a high-fat (60%) and high-calorie (520 kcal/100 g) diet. C57BL/6 mice (controls) received a standard diet. NAFLD mice and control mice were immunized with hepatitis B vaccine containing hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg). Antibody to HBsAg (anti-HBs), HBsAg and HBcAg-specific cellular immune response and functions of whole spleen cells, T lymphocytes, B lymphocytes and spleen DCs of NAFLD and control mice were assessed in vitro.


RESULTS
Levels of anti-HBs and the magnitude of proliferation of HBsAg and HBcAg-specific lymphocytes were significantly lower in NAFLD mice than control mice (P < 0.05). The spleen cells of NAFLD mice produced significantly higher levels of inflammatory cytokines (P < 0.05) and exhibited significantly increased T cell proliferation compared with control mice (P < 0.05). However, the antigen processing and presenting capacities of spleen DCs were significantly decreased in NAFLD mice compared with control mice (P < 0.05). Palmitic acid, a saturated fatty acid, caused diminished antigen processing and presenting capacity of both murine and human DCs.


CONCLUSIONS
Nonalcoholic fatty liver disease mice exhibit decreased magnitudes of antigen-specific humoral and cellular immune responses. This effect is mainly, if not solely, due to impaired antigen processing and presentation capacities of DC.
Miyake
Teruki
T
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.
Akbar
Sheikh Mohammad Fazle
SM
Yoshida
Osamu
O
Chen
Shiyi
S
Hiasa
Yoichi
Y
Matsuura
Bunzo
B
Abe
Masanori
M
Onji
Morikazu
M
D000328:Adult; D000818:Animals; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology*; D004041:Dietary Fats; D004195:Disease Models, Animal; D002149:Energy Intake; D005234:Fatty Liver / Q000276:immunology*; D005260:Female; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D013154:Spleen / Q000276:immunology
D004041:Dietary Fats; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines