| First Author | Shimada K | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 6 | Pages | e21477 |
| PubMed ID | 21731762 | Mgi Jnum | J:174428 |
| Mgi Id | MGI:5086029 | Doi | 10.1371/journal.pone.0021477 |
| Citation | Shimada K, et al. (2011) Caspase-1 dependent IL-1beta secretion is critical for host defense in a mouse model of Chlamydia pneumoniae lung infection. PLoS One 6(6):e21477 |
| abstractText | Chlamydia pneumoniae (CP) is an important human pathogen that causes atypical pneumonia and is associated with various chronic inflammatory disorders. Caspase-1 is a key component of the 'inflammasome', and is required to cleave pro-IL-1beta to bioactive IL-1beta. Here we demonstrate for the first time a critical requirement for IL-1beta in response to CP infection. Caspase-1(-)/(-) mice exhibit delayed cytokine production, defective clearance of pulmonary bacteria and higher mortality in response to CP infection. Alveolar macrophages harbored increased bacterial numbers due to reduced iNOS levels in Caspase-1(-)/(-) mice. Pharmacological blockade of the IL-1 receptor in CP infected wild-type mice phenocopies Caspase-1-deficient mice, and administration of recombinant IL-1beta rescues CP infected Caspase-1(-)/(-) mice from mortality, indicating that IL-1beta secretion is crucial for host immune defense against CP lung infection. In vitro investigation reveals that CP-induced IL-1beta secretion by macrophages requires TLR2/MyD88 and NLRP3/ASC/Caspase-1 signaling. Entry into the cell by CP and new protein synthesis by CP are required for inflammasome activation. Neither ROS nor cathepsin was required for CP infection induced inflammasome activation. Interestingly, Caspase-1 activation during CP infection occurs with mitochondrial dysfunction indicating a possible mechanism involving the mitochondria for CP-induced inflammasome activation. |
