| First Author | Patankar YR | Year | 2015 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 309 |
| Issue | 8 | Pages | L902-13 |
| PubMed ID | 26472815 | Mgi Jnum | J:318322 |
| Mgi Id | MGI:6859206 | Doi | 10.1152/ajplung.00228.2015 |
| Citation | Patankar YR, et al. (2015) Differential ASC requirements reveal a key role for neutrophils and a noncanonical IL-1beta response to Pseudomonas aeruginosa. Am J Physiol Lung Cell Mol Physiol 309(8):L902-13 |
| abstractText | The NLRC4 inflammasome is responsible for IL-1beta processing by macrophages in response to Pseudomonas aeruginosa infection. We therefore hypothesized that mice that lack ASC, an NLRC4 inflammasome adaptor protein necessary for in vitro IL-1beta production by macrophages, would be preferentially protected from a hyperinflammatory lethal challenge that is dependent on bacterial type three secretion system (T3SS) activity. We report herein that lack of ASC does not confer preferential protection in response to P. aeruginosa acute infection and that ASC(-/-) mice are capable of producing robust amounts of IL-1beta comparable with C57BL/6 mice. We now identify that neutrophils represent the ASC-independent source of IL-1beta production during the acute phases of infection both in models of acute pneumonia and peritonitis. Consequently, depletion of neutrophils in ASC(-/-) mice leads to a marked deficit in IL-1beta production in vivo. The pulmonary neutrophil IL-1beta response is predominantly dependent on caspase-1, which contrasts with data derived from ocular infection. These studies therefore identify a noncanonical mechanism of IL-1beta production by neutrophils independent of ASC and demonstrate the first physiological contribution of neutrophils as an important source of IL-1beta in response to acute P. aeruginosa infection during acute pneumonia and peritonitis. |
