Pneumolysin expression by streptococcus pneumoniae protects colonized mice from influenza virus-induced disease

Amaya I Wolf1, Maura C Strauman1, Krystyna Mozdzanowska1

  • 1The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, United States of America.

Virology
|July 8, 2014
PubMed

Insights

Streptococcus pneumoniae (Sp) colonization prior to influenza virus (IAV) infection protects mice from severe disease. The bacterial protein pneumolysin (PLY) is key to this protective effect, modulating immune responses in the lungs.

Area of Science:

  • Immunology
  • Microbiology
  • Respiratory Medicine

Background:

  • Influenza virus (IAV) infection severity varies greatly among individuals.
  • Respiratory tract (RT) microbes may influence this variability.
  • Streptococcus pneumoniae (Sp) is a common asymptomatic RT colonizer.

Purpose of the Study:

  • To investigate the impact of Sp colonization on IAV infection.
  • To identify mechanisms by which Sp influences IAV disease severity.

Main Methods:

  • A mouse co-infection model was established with Sp colonization preceding IAV infection.
  • Mutant Sp strains lacking specific virulence factors were used.
  • Immune responses, including alveolar macrophage (aMø) function and inflammatory cell recruitment, were analyzed.

Main Results:

  • Sp colonization 10 days before IAV infection protected against virus-induced morbidity and lung pathology.
  • Protection was dependent on the bacterial virulence factor pneumolysin (PLY).
  • PLY-sufficient Sp induced arginase 1 in aMø, leading to attenuated pulmonary inflammation.

Conclusions:

  • Sp colonization can be protective against IAV infection, contrary to typical secondary bacterial exacerbations.
  • Pneumolysin (PLY) mediates protection by modulating alveolar macrophage function.
  • Sp acts as a 'gatekeeper' against IAV-induced immunopathology through PLY-mediated mechanisms.