Impaired dendritic cell functions disrupt antigen-specific adaptive immune responses in mice with nonalcoholic fatty liver disease

J Gastroenterol. 2010 Aug;45(8):859-67. doi: 10.1007/s00535-010-0218-4. Epub 2010 Mar 2.

Abstract

Background/aims: 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.

MeSH terms

  • Adult
  • Animals
  • Cell Proliferation
  • Dendritic Cells / immunology*
  • Dietary Fats
  • Disease Models, Animal
  • Energy Intake
  • Fatty Liver / immunology*
  • Female
  • Hepatitis B Core Antigens / immunology*
  • Hepatitis B Surface Antigens / immunology*
  • Hepatitis B Vaccines / immunology
  • Humans
  • Immunity, Cellular
  • Immunity, Humoral
  • Leukocytes, Mononuclear / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Spleen / immunology

Substances

  • Dietary Fats
  • Hepatitis B Core Antigens
  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines