Eosinophils are a characteristic component of the inflammatory response seen in several diseases including allergic asthma and chronic obstructive pulmonary disease (COPD). After activation, eosinophil-derived products may exert pro-inflammatory effects and cause considerable tissue damage. In the present study, we investigated innate interactions between the respiratory tract pathogen non-typeable Haemophilus influenzae (NTHi) and human eosinophils. Bacterial binding to eosinophils was dependent on (1-3)--D-glucan receptors as deduced from blocking experiments using the soluble glucan derivatives laminarin and scleroglucan. In addition, expression of the -glucan receptor dectin-1 was shown in eosinophils by RT-PCR. Activation of the -glucan receptors by bacteria elicited a time and dose-dependent respiratory burst in eosinophils. NTHi caused increased expression of the pro-inflammatory chemokine IL-8 as measured by RT-PCR and ELISA. Incubation of eosinophils in the presence of NTHi for 4.5 h revealed upregulation of 245 different genes as detected by microarray. Signal transduction-related transcripts were most strongly upregulated followed by cytokine mRNAs. Our findings suggest that NTHi can induce an innate inflammatory response in eosinophils that is mainly mediated via -glucan receptors. This points to possible pathophysiologic mechanisms involving innate recognition of NTHi by eosinophils during infection of the airways, thus promoting inflammation in chronic pulmonary disease.