CCL1 released from M2b macrophages is essentially required for the maintenance of their properties

Patients with 10-30 days postburn injury are greatly susceptible to infections. M1MΦ{phonetic} (IL-10^-IL-12⁺ MΦ{phonetic}) are essential cells in host antibacterial innate immunity against MRSA infections. However, these effector cells are not easily generated in hosts who are carriers of M2bMΦ{phonetic} (IL-12^-IL-10⁺CCL1⁺LIGHT⁺ MΦ{phonetic}). M2bMΦ{phonetic} are inhibitory on M1MΦ{phonetic} generation. In this study, the antibacterial resistance of mice, 10-30 days postburn injury against MRSA infection, was improved by the modulation of M2bMΦ{phonetic} activities. Unburned mice inoculated with MΦ{phonetic} preparations from mice, 10-30 days after burn injury, were susceptible to MRSA infection, whereas unburned mice, inoculated with MΦ{phonetic} preparations from the same mice that were previously treated with CCL1 antisense ODN, were resistant to the infection. M2bMΦ{phonetic}, isolated from Day 15 burn mice, lost their M2bMΦ{phonetic} properties 3 days after cultivation under frequent medium changes, whereas their M2bMΦ{phonetic} properties remained in the same cultures supplemented with rCCL1. In cultures, MΦ{phonetic} preparations from Day 15 burn mice treated with CCL1 antisense ODN did not produce CCL1 and did convert to M1MΦ{phonetic} after heat-killed MRSA stimulation. Also, Day 15 burn mice treated with the ODN became resistant against MRSA infection. These results indicate that CCL1 released from M2bMΦ{phonetic} is essentially required for the maintenance of their properties. The increased susceptibility of mice, 10-30 days after burn injury to MRSA infection, may be controlled through the intervention of CCL1 production by M2bMΦ{phonetic} appearing in association with severe burn injuries.