Pathogenic Role of Macrophages in Intradermal Infection of Methicillin-Resistant Staphylococcus aureus in Thermally Injured Mice

Intradermal infection of methicillin-resistant Staphylococcus aureus (MRSA) in burned mice was pathogenically analyzed. An abscess was formed in normal mice intradermally infected with 10(8) CFU/mouse of MRSA, and all of these mice survived after the infection; however, abscess formation was not demonstrated to occur in burned mice similarly exposed to the pathogen, and all of these mice died within 5 days of infection. In burned mice, MRSA infected at the burn site intradermal tissues spread quickly throughout the whole body, while in normal mice, the pathogen remained localized at the infection site. Macrophages (M phi) isolated from the infection site tissues of normal mice produced interleukin-12 (IL-12) but not IL-10 and were characterized as M1M phi. These M1M phi were not isolated from the infection site tissues of burned mice. When normal-mouse infection site tissue M phi were adoptively transferred to burned mice at the MRSA infection site, an abscess formed, and the infection did not develop into sepsis. In contrast, an abscess did not form and sepsis developed in normal mice that were inoculated with burned-mouse infection site tissue M phi. These M phi produced IL-10 but not IL-12 and were characterized as M2M phi. These results indicate that abscess formation is a major mechanism of host resistance against intradermal MRSA infection. M1M phi in the tissues surrounding the infection site play a pivotal role in abscess formation; however, the abscess is not formed in burned mice where M2M phi predominate. M2M phi have been described as inhibitor cells for M phi conversion from resident M phi to M1M phi.