Synergistic stimulation of type I interferons during influenza virus coinfection promotes Streptococcus pneumoniae colonization in mice

Abstract

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.

Mycoplasma gallisepticum modifies virus shedding and immune response of Newcastle disease virus in broilers

“…Similar findings were reported when chickens were infected with H9N2 in combination with Staphylococcus aureus or Avobacterium paragallinarum or Ornithobacterium rhinotracheal (Kishida et al 2004, Pan et al 2012. Co-infection studies of influenza virus and Streptococcus pneumoniae in mice promoted bacterial colonization in the presence of viral infection (Nakamura et al 2011). We assume that MG induces considerable immune-suppression leading to enhanced replication of NDV yielding high mortality and morbidity rates under field conditions.…”

Coinfection with Streptococcus pneumoniae Modulates the B Cell Response to Influenza Virus

“…We detected prolonged and systemically increased levels of IL-6, which alone or together with type I IFNs induced by PR8 and S. pneumoniae (63,64) could account for the exaggerated ASC response in the medLN of PR8ϩSp-coinfected mice at day 10 p.i. This model is consistent with studies that demonstrated that IL-6, IFN-␥, and type I IFNs can enhance Ab responses (30,(65)(66)(67).…”

Viral–bacterial interactions in the respiratory tract

“…While crucial for viral clearance, the release of (particularly type I) IFNs appears to blunt several antibacterial responses by suppressing the expression of AMPs, macrophage and/or neutrophil recruitment and TH17 responses (Kudva et al, 2011;Lee et al, 2015;Nakamura et al, 2011;Shahangian et al, 2009). In contrast, exogenous IFN-b was found to inhibit bacterial transmigration and thus to protect mice from developing bacteraemia after instillation of S. pneumoniae, suggesting an ambiguous role for type I IFNs during (secondary) bacterial infection (LeMessurier et al, 2013).…”