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This project aims to extend the existing human airway epithelial model to enable studies on the most relevant and lethal respiratory bacterial pathogen, Streptococcus pneumoniae (SP). The primary goal of this proposal is to show the feasibility of the HAE model for pneumococcal infection. We hypothesize that this HAE model allows us to study (i) pneumococcal colonization by demonstrating the presence of SP in the apical layer, (ii) pneumococcal invasive infection by demonstrating the presence of SP in the basal layer, (iii) the transition from colonization to invasive infection by demonstrating the penetration of SP through the HAE into the basal layer, and (iv) pathogenicity of pneumococcal infection by demonstrating both cytotoxicity and inflammatory host response through an increased transcriptional activity of the HAE cells.