Inhibition of pulmonary antibacterial defense by interferon-γ during recovery from influenza infection

Sun, K., et al. 2008. Nat Med. 14, 558-564

Speaker : 阮馨怡                          Time : 13:00~14:00, Sep.17, 2008

Commentator : 林以行 老師                Place: Room 601

Abstract:

    Secondary bacterial pneumonia is one of the complications of respiratory tract infection by influenza. Previous studies have shown that prior influenza infection can enhance the susceptibility to subsequent bacterial invasion with excess morbidity and mortality.¹ Clinical secondary bacterial infection occurs during the recovery stage of influenza infection when the viruses begins to be cleared. In this study, the authors first immunized C57BL/6 intranasally with A/PR8/34 (H1N1), a mouse-adapted influenza virus strain, to examine the immune mechanisms of lung that are responsible for initial bacterial clearance. Unexpectedly, there was no difference in wild-type and B and T cell-deficient SCID and Rag2 –/– mice, indicating that initial bacterial clearance only required innate immunity. Lung alveolar macrophages (AM) that reside in normal respiratory lumen have an essential role in initial bacterial killing and act as the first line of defense against infection. The authors investigated possible immune factors participating in initial bacterial clearance. Depletion of alveolar macrophage with liposomal clodronate led to subsequent bacterial outgrowth, whereas neutrophil depletion by Ly6G-specific antibody did not alter the efficiency of initial bacterial clearance.² Furthermore, IFN-γ produced by T cells in the lung after viral infection suppressed surface expression of the class A scavenger receptor MARCO on AM. This suppression damaged AM-mediated bacterial uptake. Neutralization of IFN-γ with specific antibody, XMG1.2, could restore pulmonary innate defense,  confirming the suppressive effect of IFN-γ. In summary, this report demonstrated the mechanisms of synergy between influenza virus and Streptococcus pneumoniae.Influenza infection disrupts innate resistance to pneumococci that involves initial recognition and bacterial clearance by inducing specific adaptive immunity and IFN-γ production.

References:

1. Speshock, J. L., et al. 2007. Filamentous influenza A virus infection predisposes mice to fatal septicemia following superinfection with Streptococcus pneumoniae serotype 3. Infect. Immun. 75:3102-11.

2. Daley, J. M., et al. 2008. Use of Ly6G-specific monoclonal antibody to deplete neutrophils in mice. J. Leukoc. Biol. 83:64-70.