Role of M2b macrophages in the acceleration of bacterial translocation and subsequent sepsis in mice exposed to whole body [ 137Cs] gamma-irradiation

Makiko Kobayashi, Kiwamu Nakamura, Michael Cornforth, Fujio Suzuki

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19 Scopus citations

Abstract

The influence of whole-body gamma-irradiation on the antibacterial host defense against Enterococcus faecalis translocation was investigated. Mice irradiated with or without 5 Gy [ 137Cs] gamma-rays were orally infected with 10 6 CFU/mouse E. faecalis. The pathogen was detected in the mesenteric lymph nodes (MLNs) of irradiated mice 1-4 d postinfection, whereas E. faecalis was not isolated from MLNs of normal mice. All irradiated mice died within 5 d of infection, whereas no mortality was shown in normal mice infected with the pathogen. Irradiated mice inoculated with normal mouse MLN macrophages (Mφ) were shown to be resistant against the infection, although the same mice inoculated with irradiated mouse MLNMφ (I-MLNMφ) died postinfection. I-MLNMφ were identified as IL-10 +IL-12 -CCL1 +LIGHT + Mφ (M2bMφ) and were shown to be inhibitory on Mφ conversion from resident Mφ to IL-10 -IL-12 +Mφ (M1Mφ). M2bMφ were demonstrated in MLNs of mice 10-35 d after gamma-irradiation. M1Mφ were not induced by E. faecalis Ag in cultures of I-MLNMφ, whereas normal mouse MLNMφ were converted to M1Mφ in response to the Ag stimulation. After treatment with CCL1 antisense oligodeoxynucleotides, M2bMφ disappeared in MLNs of irradiated mice, and M1Mφ were generated in MLNs of these mice following E. faecalis stimulation. These results indicate that M2bMφ presented in the I-MLNMφ populations were responsible for the impaired resistance of mice irradiated with gamma-rays to bacterial translocation and subsequent sepsis. E. faecalis translocation and subsequent sepsis may be controlled immunologically by the intervention of M2bMφ present in MLNs.

Original languageEnglish
Pages (from-to)296-303
Number of pages8
JournalJournal of Immunology
Volume189
Issue number1
DOIs
StatePublished - Jul 1 2012

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ASJC Scopus subject areas

  • Immunology

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