Control of MRSA sepsis by CCL1 antisense ODN in severely burned mice (106.23)

Abstract

Abstract Severely burned mice are very susceptible to MRSA infection. M1Mϕ, a major effector cell in host antibacterial innate immunity, were not generated in mice 1 to 3 weeks after severe burn injury, because these mice carried M2bMϕ predominantly. Previously, CCL1 was shown to be needed to maintain M2bMϕ properties, and the elimination of M2bMϕ was demonstrated in burned mice treated with CCL1 antisense ODN. Therefore, in this study, we tried to control MRSA infection by CCL1 antisense ODN treatment in mice 1 to 3 weeks after burn injury. Burned mice (25% TBSA, 3rd degree flame burn) were treated s.c. with 10 μg/mouse of CCL1 antisense ODN twice a day for 2 days beginning 13 days after burn injury. Fourteen days after burn injury, these mice were infected i.v. with 107 CFU/mouse of MRSA. The severities of MRSA infection were evaluated by (i) the growth of the pathogen in organs and blood and (ii) their mortality rates, as compared with controls (burned mice treated with scrambled ODN). In the results, all burned mice treated with CCL1 antisense ODN survived after MRSA infection, while 83% of burned mice treated with scrambled ODN died. After infection, MRSA grew in the kidneys and blood of burned mice treated with scrambled ODN, while greatly diminished growth of the pathogen was shown in these organs of burned mice treated with CCL1 antisense ODN. These results indicate that MRSA sepsis is effectively controlled in burned mice subjected to CCL1 gene therapy.