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Protease-Activated Receptor 2 Facilitates Bacterial Dissemination in Pneumococcal Pneumonia

Florry E van den Boogaard1,2, Xanthe Brands1,2, JanWillem Duitman1,2

  • 1Center for Experimental and Molecular Medicine (CEMM), The Netherlands.

The Journal of Infectious Diseases
|February 8, 2018
PubMed

Insights

Streptococcus pneumoniae exploits Protease-Activated Receptor 2 (PAR2) to spread from the lungs. Blocking PAR2 in mice improved defense against pneumococcal pneumonia, reducing mortality and lung damage.

Area of Science:

  • Immunology
  • Microbiology
  • Pulmonology

Background:

  • Streptococcus pneumoniae is a leading cause of community-acquired pneumonia.
  • Protease-Activated Receptor 2 (PAR2) plays a role in lung inflammatory responses.
  • The specific role of PAR2 in pneumococcal pneumonia pathogenesis is not well understood.

Purpose of the Study:

  • To investigate the role of PAR2 in the host response to Streptococcus pneumoniae infection.
  • To determine if PAR2 contributes to the dissemination of S. pneumoniae from the airways.

Main Methods:

  • Pneumococcal pneumonia and sepsis models were established in wild-type and PAR2 knock-out (Par2-/-) mice.
  • Bacterial burdens, lung barrier integrity, and mortality were assessed.
  • PAR2 activation by S. pneumoniae proteases was examined in a reporter cell line.

Main Results:

  • Par2-/- mice exhibited enhanced host defense, preserved lung barrier integrity, and reduced mortality during pneumococcal pneumonia.
  • PAR2 deficiency did not affect bacterial growth following intravenous infection.
  • S. pneumoniae proteases were shown to cleave and activate PAR2, facilitating systemic dissemination.

Conclusions:

  • Streptococcus pneumoniae utilizes PAR2 to disseminate systemically from the respiratory tract.
  • Targeting PAR2 may represent a novel therapeutic strategy for pneumococcal pneumonia.

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