| First Author | Perez-Nazario N | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 9 | Pages | 4720-30 |
| PubMed ID | 24078701 | Mgi Jnum | J:206232 |
| Mgi Id | MGI:5548247 | Doi | 10.4049/jimmunol.1301679 |
| Citation | Perez-Nazario N, et al. (2013) Selective ablation of lung epithelial IKK2 impairs pulmonary Th17 responses and delays the clearance of Pneumocystis. J Immunol 191(9):4720-30 |
| abstractText | Pneumocystis is an atypical fungal pathogen that causes severe, often fatal pneumonia in immunocompromised patients. Healthy humans and animals also encounter this pathogen, but they generate a protective CD4(+) T cell-dependent immune response that clears the pathogen with little evidence of disease. Pneumocystis organisms attach tightly to respiratory epithelial cells, and in vitro studies have demonstrated that this interaction triggers NF-kappaB-dependent epithelial cell responses. However, the contribution of respiratory epithelial cells to the normal host response to Pneumocystis remains unknown. IkappaB kinase 2 (IKK2) is the upstream kinase that is critical for inducible NF-kappaB activation. To determine whether IKK2-dependent lung epithelial cell (LEC) responses contribute to the anti-Pneumocystis immune response in vivo, transgenic mice with LEC-specific deletion of IKK2 (IKK2(DeltaLEC)) were generated. Compared to wild-type mice, IKK2(DeltaLEC) mice exhibited a delayed onset of Th17 and B cell responses in the lung and delayed fungal clearance. Importantly, delayed Pneumocystis clearance in IKK2(DeltaLEC) mice was associated with an exacerbated immune response, impaired pulmonary function, and altered lung histology. These data demonstrate that IKK2-dependent LEC responses are important regulators of pulmonary adaptive immune responses and are required for optimal host defense against Pneumocystis infection. LECs likely set the threshold for initiation of the pulmonary immune response and serve to prevent exacerbated lung inflammation by promoting the rapid control of respiratory fungal infection. |
