Differential effect of prior influenza infection on alveolar macrophage phagocytosis of Staphylococcus aureus and Escherichia coli: involvement of interferon-gamma production

Abstract

The influenza A virus is one of the main causes of respiratory infection. Although influenza virus infection alone can result in pneumonia, secondary bacterial infection combined with the virus is the major cause of morbidity and mortality. Interestingly, while influenza infection increases susceptibility to some bacteria, including Streptococcus pneumoniae, Staphylococcus aureus (S. aureus), and Haemophilus influenzae, other bacteria such as Escherichia coli (E. coli) and Klebsiella pneumoniae are not associated with influenza infection. The reason for this discrepancy is not known. In this study, it was found that prior influenza virus infection inhibits murine alveolar macrophage phagocytosis of S. aureus but not of E. coli. Here, the mechanism for this inhibition is elucidated: prior influenza virus infection strongly increases interferon gamma (IFN-γ) production. Furthermore, it was shown that IFN-γ differentially affects alveolar macrophage phagocytosis of S. aureus and E. coli. The findings of the present study explain how influenza virus infection increases susceptibility to some bacteria, such as S. aureus, but not others, and provides evidence that IFN-γ might be a promising target for protecting the human population from secondary bacterial infection by influenza.

Immune Dysfunction and Bacterial Coinfections following Influenza

“…Furthermore, treatment of non-virus infected mice with exogenous IFN-γ can mimic viral infection and result in inhibition of alveolar macrophage-mediated bacterial phagocytosis (3). A critical role for IFN-γ in inhibiting phagocytosis of S. aureus by alveolar macrophages has similarly been reported (43). Further experiments showed that the relatively high levels of IFN-γ in the lung following influenza caused inhibition of MARCO expression (3), the scavenger receptor necessary for recognition of non-opsonized pneumococci by alveolar macrophages (44).…”

Linezolid Decreases Susceptibility to Secondary Bacterial Pneumonia Postinfluenza Infection in Mice Through its Effects on IFN-γ

“…In investigating this discrepancy, authors noted the increase in IFNγ concentrations following influenza A infection, and found that macrophage phagocytosis of varied bacterial strains was differentially affected by the presence of IFNγ. IFNγ inhibited macrophage phagocytosis of the gram-positive bacterium Staphylococcus aureus but failed to inhibit phagocytosis of the gram-negative pathogen E. coli (34). In accordance with other studies (15), this suggests that high IFNγ concentrations following influenza infection may contribute to hyper-susceptibility to S. pneumoniae infection by inhibiting bacterial phagocytosis by macrophages.…”

Investigation of the Effects of Emphysema and Influenza on Alveolar Sacs Closure through CFD Simulation

“…For example, airways can be blocked by a foreign object or tumors that prevent the alveolar sacs from filling with air and collapse of lung tissue can occur in the affected area. Influenza viruses are among those foreign objects that cause alveolar sac closure and they are among the most common factors that lead to human respiratory infections and cause high morbidity and mortality rate [11]. Salmon et al [12] investigated the influence of airway closure and alveolar collapse on transpulmonary pressure-volume curves under large-volume deflation and inflation.…”