Both influenza-induced neutrophil dysfunction and neutrophil-independent mechanisms contribute to increased susceptibility to a secondary Streptococcus pneumoniae infection.
Since secondary Streptococcus pneumoniae infections greatly increase the mortality of influenza infections, we determined the relative roles of neutrophil-dependent and -independent mechanisms in increased susceptibility to S. pneumoniae during influenza infection. Mice infected with influenza for 6 days, but not 3 days, showed a significant increase in susceptibility to S. pneumoniae infection compared to mice not infected with influenza. There was significant neutrophil accumulation in the lungs of S. pneumoniae-infected mice regardless of whether or not they were infected with influenza for 3 or 6 days. Depletion of neutrophils in these mice resulted in increased susceptibility to S. pneumoniae in both the non-influenza-infected mice and mice infected with influenza for 3 days but not in the mice infected with influenza for 6 days, indicating that a prior influenza infection of 6 days may compromise neutrophil function, resulting in increased susceptibility to a S. pneumoniae infection. Neutrophils from the lungs of mice infected with influenza for 3 or 6 days exhibited functional impairment in the form of decreased phagocytosis and intracellular reactive oxygen species generation in response to S. pneumoniae. In addition, neutrophil-depleted mice infected with influenza for 6 days were more susceptible to S. pneumoniae than neutrophil-depleted mice not infected with influenza, indicating that neutrophil-independent mechanisms also contribute to influenza-induced increased susceptibility to S. pneumoniae. Pulmonary interleukin-10 levels were increased in coinfected mice infected with influenza for 6 days but not 3 days. Thus, an influenza infection of 6 days increases susceptibility to S. pneumoniae by both suppression of neutrophil function and by neutrophil-independent mechanisms such as enhanced cytokine production.
McNamee
Lynnelle A
LA
Veterinary Molecular Biology Department, Montana State University, 960 Technology Blvd., Bozeman, MT 59718, USA. mcnamela@yahoo.com
Harmsen
Allen G
AG
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004198:Disease Susceptibility; D005260:Female; D007960:Leukocyte Disorders / Q000382:microbiology*; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000150:complications* / Q000276:immunology; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000382:microbiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000276:immunology
D016207:Cytokines; D017382:Reactive Oxygen Species