The goal of my proposal is to characterize the response of respiratory epithelial cells infected with PA103deltaUdeltaT a Pseudomonas aeruginosa (PA) mutant that lacks all known effectors (exoU, exoY, exoT, exoS,), but can still elicit a response in HeLa cells in the form of JNK, MAPK kinases and NF-kappaB activation. This will be achieved by 1) identifying the surveillance receptor proteins responsible for recognition, 2) defining the impact of bacterial recognition on epithelial cell biology and 3) evaluating how this response is modulated by products translocated by the Type III secretion system of PA. The approach will be to establish immortalized airway epithelial cells lines from mice lacking the recognition genes of interest, infect cells with PA mutants previously characterized in our lab, then biochemical, molecular and cellular studies will be used to evaluate the response. The experiments proposed will identify the mechanisms by which PA elicits a response from epithelial cells and the pathways that lead to it. This research will enhance an understanding of the recognition mechanisms present in epithelial cells, define an active role for epithelial cells in the immune response and provide drug targets for Pseudomonas sp infections.
| Mijares, Lilia A; Wangdi, Tamding; Sokol, Caroline et al. (2011) Airway epithelial MyD88 restores control of Pseudomonas aeruginosa murine infection via an IL-1-dependent pathway. J Immunol 186:7080-8 |
| Wangdi, Tamding; Mijares, Lilia A; Kazmierczak, Barbara I (2010) In vivo discrimination of type 3 secretion system-positive and -negative Pseudomonas aeruginosa via a caspase-1-dependent pathway. Infect Immun 78:4744-53 |
| Sutterwala, Fayyaz S; Mijares, Lilia A; Li, Li et al. (2007) Immune recognition of Pseudomonas aeruginosa mediated by the IPAF/NLRC4 inflammasome. J Exp Med 204:3235-45 |
