Article abstract
Nature Medicine 14, 558 - 564 (2008)
Published online: 27 April 2008 | doi:10.1038/nm1765
Inhibition of pulmonary antibacterial defense by interferon-
during recovery from influenza infection
Abstract
Secondary bacterial infection often occurs after pulmonary virus infection and is a common cause of severe disease in humans, yet the mechanisms responsible for this viral-bacterial synergy in the lung are only poorly understood. We now report that pulmonary interferon-
(IFN-) produced during T cell responses to influenza infection in mice inhibits initial bacterial clearance from the lung by alveolar macrophages. This suppression of phagocytosis correlates with lung IFN- abundance, but not viral burden, and leads to enhanced susceptibility to secondary pneumococcal infection, which can be prevented by IFN- neutralization after influenza infection. Direct inoculation of IFN- can mimic influenza infection and downregulate the expression of the class A scavenger receptor MARCO on alveolar macrophages. Thus, IFN-, although probably facilitating induction of specific anti-influenza adaptive immunity, suppresses innate protection against extracellular bacterial pathogens in the lung.
- Center for Immunology & Microbial Disease, Albany Medical College, 47 New Scotland Avenue, Albany, New York 12208, USA.
Correspondence to: Dennis W Metzger1 e-mail: metzged@mail.amc.edu