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2011 ; 121
(9
): 3657-65
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Synergistic stimulation of type I interferons during influenza virus coinfection
promotes Streptococcus pneumoniae colonization in mice
#MMPMID21841308
Nakamura S
; Davis KM
; Weiser JN
J Clin Invest
2011[Sep]; 121
(9
): 3657-65
PMID21841308
show ga
Pneumococcal infection of the respiratory tract is often secondary to recent
influenza virus infection and accounts for much of the morbidity and mortality
during seasonal and pandemic influenza. Here, we show that coinfection of the
upper respiratory tract of mice with influenza virus and pneumococcus leads to
synergistic stimulation of type I IFNs and that this impairs the recruitment of
macrophages, which are required for pneumococcal clearance, due to decreased
production of the chemokine CCL2. Type I IFN expression was induced by
pneumococcal colonization alone. Colonization followed by influenza coinfection
led to a synergistic type I IFN response, resulting in increased density of
colonizing bacteria and susceptibility to invasive infection. This enhanced type
I IFN response inhibited production of the chemokine CCL2, which promotes the
recruitment of macrophages and bacterial clearance. Stimulation of CCL2 by
macrophages upon pneumococcal infection alone required the pattern recognition
receptor Nod2 and expression of the pore-forming toxin pneumolysin. Indeed, the
increased colonization associated with concurrent influenza virus infection was
not observed in mice lacking Nod2 or the type I IFN receptor, or in mice
challenged with pneumococci lacking pneumolysin. We therefore propose that the
synergistic stimulation of type I IFN production during concurrent influenza
virus and pneumococcal infection leads to increased bacterial colonization and
suggest that this may contribute to the higher rates of disease associated with
coinfection in humans.