Interleukin-1 Promotes Coagulation, Which Is Necessary for Protective Immunity in the Lung Against Streptococcus pneumoniae Infection

• Published in: The Journal of infectious diseases 2013-01, Vol.207 (1), p.50-60
• Main Authors: Yang, Hyungjun, Ko, Hyun-Jeong, Yang, Jin-Young, Kim, Jae-Jin, Seo, Sang-Uk, Park, Seung Gu, Choi, Sun Shim, Seong, Je Kyung, Kweon, Mi-Na
• Format: Article
• Language: English
• Subjects: Animals; Bacteria; Bacterial diseases; Biological and medical sciences; Blood Coagulation - immunology; Coagulation; Cytokines; Disease Susceptibility; Down-Regulation; Fibrinogen - metabolism; Fundamental and applied biological sciences. Psychology; Human bacterial diseases; Immunity, Innate; Infections; Infectious diseases; Interleukin-1 - immunology; Lung - immunology; Lung - metabolism; Lung - microbiology; Lungs; Medical sciences; Mice; Mice, Inbred C57BL; Microbiology; Mutation; Neutrophils; Neutrophils - immunology; Pneumococcal infections; Pneumococcal pneumonia; 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; Staphylococcal infections, streptococcal infections, pneumococcal infections; Streptococcus pneumoniae; Streptococcus pneumoniae - drug effects; Streptococcus pneumoniae - immunology; Survival Analysis; Thrombin - metabolism
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jis651

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.