| First Author | Pires S | Year | 2018 |
| Journal | Eur J Immunol | Volume | 48 |
| Issue | 10 | Pages | 1707-1716 |
| PubMed ID | 30051912 | Mgi Jnum | J:266420 |
| Mgi Id | MGI:6201483 | Doi | 10.1002/eji.201847556 |
| Citation | Pires S, et al. (2018) IL-1beta activation in response to Staphylococcus aureus lung infection requires inflammasome-dependent and independent mechanisms. Eur J Immunol 48(10):1707-1716 |
| abstractText | Maintaining balanced levels of IL-1beta is extremely important to avoid host tissue damage during infection. Our goal was to understand the mechanisms behind the reduced pathology and decreased bacterial burdens in Ifnlr1(-/-) mice during lung infection with Staphylococcus aureus. Intranasal infection of Ifnlr1(-/-) mice with S. aureus led to significantly improved bacterial clearance, survival and decrease of proinflammatory cytokines in the airway including IL-1beta. Ifnlr1(-/-) mice treated with recombinant IL-1beta displayed increased bacterial burdens in the airway and lung. IL-1beta levels in neutrophils from Ifnlr1(-/-) infected mice lungs were decreased when compared to neutrophils from WT mice. Mice lacking NLRP3 and caspase-1 had reduced IL-1beta levels 4 h after infection, due to reductions or absence of active caspase-1 respectively, but levels at 24 h were comparable to WT infected mice. Ifnlr1(-/-) infected mice had decreases in both active caspase-1 and neutrophil elastase indicating an important role for the neutrophil serine protease in IL-1beta processing. By inhibiting neutrophil elastase, we were able to decrease IL-1beta levels by 39% in Nlrp3(-/-) infected mice when compared to WT mice. These results highlight the crucial role of both proteases in IL-1beta processing, via inflammasome-dependent and -independent mechanisms. |
