Intranasal interleukin-12 treatment for protection against respiratory infection with methicillin-resistant Staphylococcus aureus. (INC7P.413)

Abstract

Abstract Methicillin-resistant Staphylococcus aureus (MRSA) represents the most common pathogen associated with nosocomial pneumonia. In the present study, the role of interleukin-12 (IL-12) in inducing protective immunity in the lungs against intranasal infection of mice with MRSA was investigated. It was found that IL-12-deficient mice showed a lower survival rate, a higher bacterial burden in both the lung and spleen, and a lower level of interferon gamma (IFN-γ) in the lung than wild-type (WT) mice. These effects were completely reversed by replacement therapy with recombinant IL-12. Furthermore, exogenous IL-12 treatment of WT mice 24 h before intranasal infection with a lethal dose of MRSA significantly improved bacterial clearance and resulted in protection from death. These IL-12 treated-mice had a greater number of the lung natural killer (NK) cells and neutrophils, and had higher levels of IFN-γ in the lung and serum compared to control mice. The majority of IFN-γ-producing cells detected in IL-12-treated mice were NK cells. IL-12-induced protection against MRSA infection was abolished in NK cell-depleted, IFN-γ deficient, and MIIG mice. In addition, we found that combination therapy with linezolid and IL-12 following intranasal infection with MRSA significantly increased survival compared to mice receiving linezolid or IL-12 alone. Our results indicate that IL-12 can play an important role in protection against MRSA infection.