M2b monocytes provoke bacterial pneumonia and gut bacteria-associated sepsis in alcoholics

Yusuke Tsuchimoto, Akira Asai, Yasuhiro Tsuda, Ichiaki Ito, Tomoki Nishiguchi, Melanie C. Garcia, Sumihiro Suzuki, Makiko Kobayashi, Kazuhide Higuchi, Fujio Suzuki

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Chronic alcohol consumption markedly impairs host antibacterial defense against opportunistic infections. g-irradiated NOD-SCID IL-2Rgnull mice inoculated with nonalcoholic PBMCs (control PBMC chimeras) resisted Klebsiella pneumonia and gut bacteriaassociated sepsis, whereas the chimeras created with alcoholic PBMCs (alcoholic PBMC chimeras) were very susceptible to these infections. M1 monocytes (IL-12+IL-102CD1632CD14+ 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-122IL-102CCL12CD1632CD14+ 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.

Original languageEnglish (US)
Pages (from-to)5169-5177
Number of pages9
JournalJournal of Immunology
Volume195
Issue number11
DOIs
StatePublished - Dec 1 2015

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Bacterial Pneumonia
Alcoholics
Monocytes
Sepsis
Bacteria
Oligodeoxyribonucleotides
Infection
Macrophages
Phenotype
Lung
Opportunistic Infections
Klebsiella pneumoniae
Interleukin-12
Innate Immunity
Alcohol Drinking
Alcoholism
Pneumonia
Cell Culture Techniques

ASJC Scopus subject areas

  • Immunology

Cite this

M2b monocytes provoke bacterial pneumonia and gut bacteria-associated sepsis in alcoholics. / Tsuchimoto, Yusuke; Asai, Akira; Tsuda, Yasuhiro; Ito, Ichiaki; Nishiguchi, Tomoki; Garcia, Melanie C.; Suzuki, Sumihiro; Kobayashi, Makiko; Higuchi, Kazuhide; Suzuki, Fujio.

In: Journal of Immunology, Vol. 195, No. 11, 01.12.2015, p. 5169-5177.

Research output: Contribution to journalArticle

Tsuchimoto, Y, Asai, A, Tsuda, Y, Ito, I, Nishiguchi, T, Garcia, MC, Suzuki, S, Kobayashi, M, Higuchi, K & Suzuki, F 2015, 'M2b monocytes provoke bacterial pneumonia and gut bacteria-associated sepsis in alcoholics', Journal of Immunology, vol. 195, no. 11, pp. 5169-5177. https://doi.org/10.4049/jimmunol.1501369
Tsuchimoto, Yusuke ; Asai, Akira ; Tsuda, Yasuhiro ; Ito, Ichiaki ; Nishiguchi, Tomoki ; Garcia, Melanie C. ; Suzuki, Sumihiro ; Kobayashi, Makiko ; Higuchi, Kazuhide ; Suzuki, Fujio. / M2b monocytes provoke bacterial pneumonia and gut bacteria-associated sepsis in alcoholics. In: Journal of Immunology. 2015 ; Vol. 195, No. 11. pp. 5169-5177.
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AU - Garcia, Melanie C.

AU - Suzuki, Sumihiro

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AU - Higuchi, Kazuhide

AU - Suzuki, Fujio

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