Enterococcus faecalis translocation in mice with severe burn injury: a pathogenic role of CCL2 and alternatively activated macrophages (M2aMϕ and M2cMϕ)

Abstract Early after burn injury, CCL2 converts resident mesenteric lymph node macrophages to M2a and M2c macrophages that decrease host antibacterial innate immunity against sepsis stemming from Enterococcus faecalis Here, we investigated a role of CCL2 on the increased susceptibility of severely burned mice to Enterococcus faecalis translocation. After inoculation of Mϕ from MLMϕ of normal mice, 80% of the SCIDbgMN mice orally infected with the lethal dose of E. faecalis survived, and all mice inoculated with MLMϕ from thermally injured mice died. At this time, SCIDbgMN mice inoculated with MLMϕ from thermally injured CCL2−/− mice were shown to be resistant (90% survival). M1Mϕ were not induced by E. faecalis antigen in cultures of MLMϕ from thermally injured wild-type mice, and MLMϕ from thermally injured CCL2−/− mice converted to M1Mϕ after the antigen stimulation. MLMϕ from wild-type mice 2 days postburn injury possessed M2a- and M2cMϕ properties, and those from mice 7–21 days postburn injury carried M2bMϕ properties. However, MLMϕ from thermally injured CCL2−/− mice did not show any typical properties for M2a- or M2cMϕ. CCL17 and CXCL13 (biomarkers for M2a- and M2cMϕ), but not CCL1 (a biomarker of M2bMϕ), were produced by MLMϕ from thermally injured CCL2−/− mice treated with rCCL2. These results indicate that CCL2 converts resident MLMϕ to M2a- and M2cMϕ, detected early after burn injury, and decreases host antibacterial innate immunity against sepsis stemming from oral E. faecalis infection.