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

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.

• Authors: Teruki Miyake, Sheikh Mohammad Fazle Akbar, Osamu Yoshida, Shiyi Chen, Yoichi Hiasa, Bunzo Matsuura, Masanori Abe, Morikazu Onji
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 45 Issue 8 Pg. 859-67 (Aug 2010) ISSN: 1435-5922 [Electronic] Japan
• PMID: 20195647 (Publication Type: Journal Article)

Chemical References

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

Topics

• 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)