Role of M2b Macrophages in the Acceleration of Bacterial Translocation and Subsequent Sepsis in Mice Exposed to Whole Body [137Cs] Gamma-Irradiation

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 106 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.

M2b Monocytes Provoke Bacterial Pneumonia and Gut Bacteria–Associated Sepsis in Alcoholics

“…In our previous murine studies, CCL1 produced by M2b macrophages was an essential chemokine for the survival of M2b macrophages (30); when these cells were cultured with an inhibitor of CCL1 production (single-stranded nucleic acid, CCL1 antisense ODN); they reverted to quiescent macrophages (30,31 (Fig. 5A), and they produced IL-12 under Ag stimulation (Fig.…”

“…In our previous murine studies (29,31), the major host defense effector cells in fighting against these infections were characterized as M1 macrophages (IL-10 2 IL-12 + CD163 2 macrophages).…”

“…M2b macrophages were shown to inhibit the conversion of quiescent macrophages to M1 macrophages. CCL1 was shown to be essential for the prolongation of M2b macrophages (30), and M2b macrophages were reverted to quiescent macrophages posttreatment with CCL1 antisense oligodeoxynucleotide (ODN) (30,31). The increased susceptibility of CAC mice to bacterial pneumonia and sepsis stemming from enterococcal translocation was improved to a level shown in normal mice posttreatment with CCL1 antisense ODN (29).…”

“…Enterococcal translocation. Both groups of chimeras were infected orally with E. faecalis after decontamination with a mixture of three antibiotics and oral treatment with a proton-pump inhibitor (lansoprazole), as previously described (29,31). In decontaminated mice, the numbers of microbiota in the gut were negligibly small.…”

The Polarization of M2b Monocytes in Cultures of Burn Patient Peripheral CD14+Cells Treated with a Selected Human CCL1 Antisense Oligodeoxynucleotide

“…In our studies [10][11][12], mouse M2bMf polarized to quiescent Mf after treatment with an M2bMf polarizer, murine CCL1 antisense oligodeoxynucleotide (ODN). CCL1 has already been characterized as an essential chemokine for the maintenance of M2bMf properties [10].…”