| First Author | Ahn D | Year | 2019 |
| Journal | Am J Respir Cell Mol Biol | Volume | 60 |
| Issue | 2 | Pages | 158-166 |
| PubMed ID | 30183325 | Mgi Jnum | J:288292 |
| Mgi Id | MGI:6416780 | Doi | 10.1165/rcmb.2018-0021OC |
| Citation | Ahn D, et al. (2019) The Effects of IFN-lambda on Epithelial Barrier Function Contribute to Klebsiella pneumoniae ST258 Pneumonia. Am J Respir Cell Mol Biol 60(2):158-166 |
| abstractText | IFN-lambda and IL-22, cytokines that share the coreceptor IL-10RB, are both induced over the course of Klebsiella pneumoniae ST258 (KP35) pneumonia. IL-22 is known to protect mucosal barriers, whereas the effects of IFN-lambda on the mucosa are not established. We postulated that IFN-lambda plays a role in regulating the airway epithelial barrier to facilitate cellular trafficking to the site of infection. In response to IFN-lambda, the transmigration of neutrophils across a polarized monolayer of airway epithelial cells was increased, consistent with diminished epithelial integrity. KP35 infection increased epithelial permeability, and pretreatment with IFN-lambda amplified this effect and facilitated bacterial transmigration. These effects of IFN-lambda were confirmed in vivo, in that mice lacking the receptor for IFN-lambda (Ifnlr1(-/-)) were protected from bacteremia in a murine model of KP35 pneumonia. Conversely, the integrity of the epithelial barrier was protected by IL-22, with subsequent impairment of neutrophil and bacterial transmigration in vitro. Maximal expression of IL-22 in vivo was observed later in the course of infection than IFN-lambda production, with high levels of IL-22 produced by recruited immune cells at 48 hours, consistent with a role in epithelial barrier recovery. The divergent and opposing expression of these two related cytokines suggests a regulated interaction in the host response to KP35 infection. A major physiological effect of IFN-lambda signaling is a decrease in epithelial barrier integrity, which facilitates immune cell recruitment but also enables K. pneumoniae invasion. |
