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Pulmonary antibacterial defenses during mild and severe influenza virus infection
1Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland 21209.
Abstract:
Severe influenza virus infections with pneumonic involvement are known to predispose the lungs to bacterial superinfections due to dysfunctions in the alveolar macrophage (AM) phagocytic system. To determine whether milder forms of influenza without pneumonic involvement have a similar outcome, pulmonary antibacterial defenses and AM phagocytosis were compared in murine models of mild and severe influenza virus A/HK/68 infections. Bactericidal activity was quantitated by the intrapulmonary killing of Staphylococcus aureus following aerosol challenge, whereas the functional capacity of the AMs was determined by Fc-receptor-mediated phagocytosis. With the severe virus infection, maximal suppression of bactericidal activity occurred on day 8 of infection and correlated with impairment of AM phagocytosis. A lesser but significant degree of suppression of pulmonary antibacterial defenses and AM phagocytosis was observed on the third day of the mild virus infection. The data demonstrate that mild influenza virus infections that are limited to the upper respiratory tract also impair pulmonary antibacterial defenses and may predispose the lungs to bacterial superinfections.
Insights
Even mild influenza virus infections impair lung antibacterial defenses and alveolar macrophage function, increasing susceptibility to bacterial superinfections. This study highlights risks beyond severe pneumonia.
Area of Science:
- Immunology
- Infectious Diseases
- Pulmonary Medicine
Background:
- Severe influenza with pneumonia compromises lung antibacterial defenses by impairing alveolar macrophage (AM) phagocytosis.
- The impact of milder influenza infections on pulmonary antibacterial capacity remains less understood.
Purpose of the Study:
- To investigate if mild influenza virus infections, without pneumonic involvement, also lead to impaired pulmonary antibacterial defenses.
- To compare the effects of mild versus severe influenza on AM phagocytic function and lung bacterial killing capacity.
Main Methods:
- Murine models were infected with influenza A/HK/68 (mild and severe forms).
- Pulmonary antibacterial activity was assessed by intrapulmonary killing of Staphylococcus aureus.
- Alveolar macrophage (AM) phagocytic capacity was measured via Fc-receptor-mediated phagocytosis.
Main Results:
- Severe influenza infection significantly suppressed AM phagocytosis and pulmonary bactericidal activity by day 8.
- Mild influenza infection also caused a significant, albeit lesser, suppression of pulmonary antibacterial defenses and AM phagocytosis by day 3.
- These impairments occurred even in the absence of pneumonic involvement.
Conclusions:
- Mild influenza virus infections, limited to the upper respiratory tract, can impair pulmonary antibacterial defenses.
- Dysfunctional alveolar macrophage phagocytosis following mild influenza may predispose the lungs to secondary bacterial infections.
- Influenza's impact on host defense extends beyond severe pneumonic cases.