title: M2b macrophage elimination and improved resistance of mice with chronic alcohol consumption to opportunistic infections.
abstract: 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.
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan.
authors.forename: Hideko
authors.initials: H
authors.lastname: Ohama
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Asai
authors.affiliation: Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas.
authors.forename: Ichiaki
authors.initials: I
authors.lastname: Ito
authors.affiliation: Department of Biostatistics and Epidemiology, University of North Texas Health Science Center, Fort Worth, Texas.
authors.forename: Sumihiro
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas.
authors.forename: Makiko
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Higuchi
authors.affiliation: Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas. Electronic address: fsuzuki@utmb.edu.
authors.forename: Fujio
authors.initials: F
authors.lastname: Suzuki
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects / Q000276:immunology* / Q000473:pathology; D000818:Animals; D054402:Chemokine CCL1 / Q000037:antagonists & inhibitors / Q000276:immunology; D016983:Enterococcus / Q000276:immunology; D016908:Gram-Positive Bacterial Infections / Q000276:immunology* / Q000473:pathology; D007113:Immunity, Innate; D007709:Klebsiella / Q000276:immunology; D007710:Klebsiella Infections / Q000276:immunology* / Q000473:pathology; D008264:Macrophages; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D009894:Opportunistic Infections / Q000276:immunology* / Q000473:pathology; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000473:pathology
chemical_list: C502258:Ccl1 protein, mouse; D054402:Chemokine CCL1; D020319:Oligodeoxyribonucleotides, Antisense