Interleukin-1 promotes coagulation, which is necessary for protective immunity in the lung against Streptococcus pneumoniae infection

J Infect Dis. 2013 Jan 1;207(1):50-60. doi: 10.1093/infdis/jis651. Epub 2012 Oct 24.

Abstract

Interleukin (IL)-1 is a well-known cytokine for the initiation of innate immunity in bacterial infection. However, the underlying mechanism of IL-1 on the respiratory infection is not fully elucidated. We studied how IL-1 contributes to the host defense against Streptococcus pneumoniae. IL-1R(-/-) mice showed high mortality, local cytokine storm, and substantial infiltrates in the lower respiratory tract after intratracheal challenge with S. pneumoniae. The IL-1-deficient condition did not suppress the propagation of bacteria in the lung, although the recruitment and the bacteria-killing ability of neutrophils (CD11b(+)Ly6C(+)Ly6G(+)) were not defective compared with wild-type mice. Unexpectedly, we found that the transcription of fibrinogen alpha and gamma genes were highly activated in the lungs of wild-type mice after the infection, whereas no significant changes were found in IL-1R(-/-) mice. Of note, synthesis of fibrinogen was dependent on the IL-1-IL-6-Stat3 cascade. Treatment with recombinant fibrinogen improved survival and bacterial propagation in the IL-1R(-/-) mice and blockade of the coagulation increased the susceptibility of wild-type mice to pneumococcal pneumonia. Our findings suggest that IL-1 signaling leads to the synthesis of fibrinogen in the lung after pneumococcus infection and is followed by coagulation, which contributes to the control of bacterial infection in the pulmonary tract.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Coagulation / immunology*
  • Disease Susceptibility
  • Down-Regulation
  • Fibrinogen / metabolism
  • Immunity, Innate
  • Interleukin-1 / immunology*
  • Lung / immunology*
  • Lung / metabolism
  • Lung / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • Neutrophils / immunology
  • Pneumonia, Pneumococcal / drug therapy
  • Pneumonia, Pneumococcal / immunology*
  • Pneumonia, Pneumococcal / microbiology
  • Pneumonia, Pneumococcal / mortality
  • Receptors, Interleukin-1 / genetics
  • Receptors, Interleukin-1 / metabolism
  • Recombinant Proteins
  • Signal Transduction
  • Specific Pathogen-Free Organisms
  • Streptococcus pneumoniae / drug effects
  • Streptococcus pneumoniae / immunology*
  • Survival Analysis
  • Thrombin / metabolism

Substances

  • Interleukin-1
  • Receptors, Interleukin-1
  • Recombinant Proteins
  • Fibrinogen
  • Thrombin