Haemophilus influenzae stimulates ICAM-1 expression on respiratory epithelial cells

Epithelial cells interact directly with bacteria in the environment and pla y a critical role in airway defense against microbial pathogens, In this st udy, we examined the response of respiratory epithelial cells to infection with nontypable Haemophilus influenzae. Using an in vitro cell culture mode l, we found that epithelial cell monolayers released significant quantities of IL-g and expressed increased levels of ICAM-1 mRNA and surface protein in response to H. influenzae. In contrast, levels of IL-1 beta, TNF-alpha a nd MHC class I were not significantly affected, suggesting preferential act ivation of a specific subset of epithelial genes directed toward defense ag ainst bacteria. Induction of ICAM-1 required direct bacterial interaction w ith the epithelial cell surface and was not reproduced by purified H, influ enzae lipooligosaccharide. Consistent with a functional role for this respo nse, induction of ICAM-1 by H. influenzae mediated increased neutrophil adh erence to the epithelial cell surface. Furthermore, in an in vivo murine mo del of airway infection with H. influenzae, increased epithelial cell ICAM- 1 expression coincided with increased chemokine levels and neutrophil recru itment in the airway. These results indicate that ICAM-1 expression on huma n respiratory epithelial cells is induced by epithelial cell interaction wi th H. influenzae and suggest that an ICAM-1-dependent mechanism can mediate neutrophil adherence to these cells independent of inflammatory mediator r elease by other cell types, Direct induction of specific epithelial cell ge nes (such as ICAM-1 and IL-8) by bacterial infection may allow for rapid an d efficient innate defense in the airway.