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

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.