M2b Macrophage Elimination and Improved Resistance of Mice with Chronic Alcohol Consumption to Opportunistic Infections

被引:65
作者
Ohama, Hideko [1 ]
Asai, Akira [1 ]
Ito, Ichiaki [2 ]
Suzuki, Sumihiro [3 ]
Kobayashi, Makiko [2 ]
Higuchi, Kazuhide [1 ]
Suzuki, Fujio [2 ]
机构
[1] Osaka Med Coll, Dept Internal Med 2, Takatsuki, Osaka 569, Japan
[2] Univ Texas Med Branch, Dept Internal Med, Galveston, TX 77555 USA
[3] Univ N Texas, Hlth Sci Ctr, Dept Biostat & Epidemiol, Ft Worth, TX USA
关键词
BACTERIAL TRANSLOCATION; IMMUNE-COMPLEXES; APOPTOTIC CELLS; INNATE IMMUNITY; KUPFFER CELLS; LIVER-DISEASE; PHAGOCYTOSIS; POLARIZATION; ACTIVATION; GAMMA;
D O I
10.1016/j.ajpath.2014.09.022
中图分类号
R36 [病理学];
学科分类号
100103 [病原生物学];
摘要
Alcohol abuse was found to predispose persons to opportunistic infections. In this study, we tried to improve the host antibacterial resistance of chronic alcohol-consuming (CAC) mice to opportunistic infections. Bactericidal macrophages with functions to produce IL-12 and to express mRNAs for CXCL9 and inducible nitric oxide synthase (M1 macrophages) were characterized as the main effector cells in host antibacterial innate immunities against infections with opportunistic pathogens. However, CAC mice were found to be carriers of M2b macrophages [macrophages with functions to produce IL-10 and to express mRNAs for CD163, chemokine ligand (CCL)1, and LIGHT (homologous to Lymphotoxin, exhibits inducible expression, competes with herpes simplex virus glycoprotein D for high-voltage electron microscopy on T cells)], which were inhibitory on macrophage conversion from resident macrophages to M1 macrophages. Under treatment with CCL1 antisense oligodeoxynucleotides, a specific inhibitor of M2b macrophages, CAC mouse macrophages reverted to resident macrophages, and M1 macrophages were induced by a bacterial antigen from macrophages of CAC mice that were previously treated with the oligodeoxynucleotides. Opportunistic infections (enterococcal translocation and Klebsiella pneumonia) in CAC mice were completely controlled by CCL1 antisense oligodeoxynucleotides. These results indicate that certain opportunistic infections in alcoholics are controllable through the modulation of M2b macrophages.
引用
收藏
页码:420 / 431
页数:12
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