title: M2b Monocytes Provoke Bacterial Pneumonia and Gut Bacteria-Associated Sepsis in Alcoholics.
abstract: Chronic alcohol consumption markedly impairs host antibacterial defense against opportunistic infections. γ-irradiated NOD-SCID IL-2Rγ(null) mice inoculated with nonalcoholic PBMCs (control PBMC chimeras) resisted Klebsiella pneumonia and gut bacteria-associated sepsis, whereas the chimeras created with alcoholic PBMCs (alcoholic PBMC chimeras) were very susceptible to these infections. M1 monocytes (IL-12(+)IL-10(-)CD163(-)CD14(+) cells), major effector cells in antibacterial innate immunity, were not induced by a bacterial Ag in alcoholic PBMC cultures, and M2b monocytes (CCL1(+)CD163(+)CD14(+) cells), which predominated in alcoholic PBMCs, were shown to be inhibitor cells on the Ag-stimulated monocyte conversion from quiescent monocytes to M1 monocytes. CCL1, which functions to maintain M2b macrophage properties, was produced by M2b monocytes isolated from alcoholic PBMCs. These M2b monocytes reverted to quiescent monocytes (IL-12(-)IL-10(-)CCL1(-)CD163(-)CD14(+) cells) in cultures supplemented with CCL1 antisense oligodeoxynucleotide, and the subsequent quiescent monocytes easily converted to M1 monocytes under bacterial Ag stimulation. Alcoholic PBMC chimeras treated with CCL1 antisense oligodeoxynucleotide were resistant against pulmonary infection by K. pneumoniae and sepsis stemming from enterococcal translocation. These results indicate that a majority of monocytes polarize to an M2b phenotype in association with alcohol abuse, and this polarization contributes to the increased susceptibility of alcoholics to gut and lung infections. Bacterial pneumonia and gut bacteria-associated sepsis, frequently seen in alcoholics, can be controlled through the polarization of macrophage phenotypes.
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, Takatsuki 569-8686, Japan;
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tsuchimoto
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, Takatsuki 569-8686, Japan;
authors.forename: Akira
authors.identifier: http://orcid.org/0000-0001-6028-9561
authors.initials: A
authors.lastname: Asai
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, Takatsuki 569-8686, Japan;
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsuda
authors.affiliation: Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 77555; and.
authors.forename: Ichiaki
authors.initials: I
authors.lastname: Ito
authors.affiliation: Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 77555; and.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Nishiguchi
authors.affiliation: Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 77555; and.
authors.forename: Melanie C
authors.initials: MC
authors.lastname: Garcia
authors.affiliation: Department of Biostatistics, University of North Texas Health Science Center, Fort Worth, TX 76107.
authors.forename: Sumihiro
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 77555; and.
authors.forename: Makiko
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, Takatsuki 569-8686, Japan;
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Higuchi
authors.affiliation: Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 77555; and fsuzuki@utmb.edu.
authors.forename: Fujio
authors.initials: F
authors.lastname: Suzuki
mesh_terms: D000328:Adult; D057229:Alcoholics; D000437:Alcoholism / Q000276:immunology; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D002478:Cells, Cultured; D054402:Chemokine CCL1 / Q000235:genetics; D002678:Chimera / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology; D013293:Enterococcus faecalis / Q000276:immunology; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000276:immunology; D016908:Gram-Positive Bacterial Infections / Q000276:immunology / Q000382:microbiology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007710:Klebsiella Infections / Q000276:immunology / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics; D009894:Opportunistic Infections / Q000276:immunology*; D010641:Phenotype; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology; D018805:Sepsis / Q000276:immunology* / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; C065971:CCL1 protein, human; D054402:Chemokine CCL1; D020319:Oligodeoxyribonucleotides, Antisense