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

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 [Cs-137] 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 (M phi) were shown to be resistant against the infection, although the same mice inoculated with irradiated mouse MLNM phi (I-MLNM phi) died postinfection. I-MLNM phi were identified as IL-10(+)IL-12(-)CCL1(+)LIGHT(+) M phi (M2bM phi) and were shown to be inhibitory on M phi conversion from resident M phi to IL-10(-)IL-12(+)M phi (M1M phi). M2bM phi were demonstrated in MLNs of mice 10-35 d after gamma-irradiation. M1M phi were not induced by E. faecalis Ag in cultures of I-MLNM phi, whereas normal mouse MLNM phi were converted to M1M phi in response to the Ag stimulation. After treatment with CCL1 antisense oligodeoxynucleotides, M2bM phi disappeared in MLNs of irradiated mice, and M1M phi were generated in MLNs of these mice following E. faecalis stimulation. These results indicate that M2bM phi presented in the I-MLNM phi 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 M2bM phi present in MLNs. The Journal of Immunology, 2012, 189: 296-303.