Role of M2b macrophages in the acceleration of bacterial translocation and subsequent sepsis in mice exposed to whole body [137Cs] γ-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 [(137)Cs] 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) were shown to be resistant against the infection, although the same mice inoculated with irradiated mouse MLNM (I-MLNM) died postinfection. I-MLNM were identified as IL-10(+)IL-12(-)CCL1(+)LIGHT(+) M (M2bM) and were shown to be inhibitory on M conversion from resident M to IL-10(-)IL-12(+)M (M1M). M2bM were demonstrated in MLNs of mice 10-35 d after gamma-irradiation. M1M were not induced by E. faecalis Ag in cultures of I-MLNM, whereas normal mouse MLNM were converted to M1M in response to the Ag stimulation. After treatment with CCL1 antisense oligodeoxynucleotides, M2bM disappeared in MLNs of irradiated mice, and M1M were generated in MLNs of these mice following E. faecalis stimulation. These results indicate that M2bM presented in the I-MLNM 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 present in MLNs.
Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA.
Makiko
M
Kobayashi
Kiwamu
K
Nakamura
Michael
M
Cornforth
Fujio
F
Suzuki
D000818:Animals; D016470:Bacteremia / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D018988:Bacterial Translocation / Q000276:immunology* / Q000528:radiation effects; D013293:Enterococcus faecalis / Q000276:immunology* / Q000528:radiation effects; D005720:Gamma Rays; D016908:Gram-Positive Bacterial Infections / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology* / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D013997:Time Factors