Bordetella pertussis, the causative agent of whooping cough, has many well-studied virulence factors and a characteristic clinical presentation. Despite this information, it is not clear how B. pertussis interaction with host cells leads to disease. In this study, we examined the interaction of B. pertussis with a human bronchial epithelial cell line (BEAS-2B) and measured host transcriptional profiles by using high-density DNA microarrays. The early transcriptional response to this pathogen is dominated by altered expression of cytokines, DNA-binding proteins, and NFB-regulated genes. This previously unrecognized response to B. pertussis was modified in similar but nonidentical fashions by the antiinflammatory agents dexamethasone and sodium salicylate. Cytokine protein expression was confirmed, as was neutrophil chemoattraction. We show that B. pertussis induces mucin gene transcription by BEAS-2B cells then counters this defense by using mucin as a binding substrate. A set of genes is described for which the catalytic activity of pertussis toxin is both necessary and sufficient to regulate transcription. Host genomic transcriptional profiling, in combination with functional assays to evaluate subsequent biological events, provides insight into the complex interaction of host and pathogen. Bordetella pertussis is a Gram-negative coccobacillus and the causative agent of whooping cough in humans. It is a well-studied pathogen with a number of potent virulence factors. However, little is known about the responses elicited by this organism in human cells, especially at the level of gene transcription.Autopsy studies of pertussis victims performed in the early 20th century revealed a diffuse bronchopneumonia with increased secretion of mucus, associated with airway plugging and atelectasis (1). Bacteria were seen tightly packed between the cilia of epithelial cells, which desquamated during infection. Rodent models of Bordetella pertussis infection have revealed infiltrates of monocytes, neutrophils, and lymphocytes in the lung (2).B. pertussis expresses several virulence factors directed at the host epithelium. Filamentous hemagglutinin is the major adhesin of B. pertussis for bronchial epithelial cells (3). B. pertussis also produces several toxins, including pertussis toxin (PT). PT is associated with a panoply of biological effects, many of which are linked to its ADP-ribosyltransferase activity. ADP ribosylation of the G␣ family of host proteins prevents their usual regulatory response to G-protein-linked receptor engagement (4). B. pertussis also secretes an adenylate cyclase toxin that enters host cells and raises intracellular cAMP concentrations (5). Tracheal cytotoxin (TCT), a muramyl tetrapeptide bacterial cell wall fragment, in combination with lipopolysaccharide, paralyzes respiratory epithelial cilia and ultimately causes cell death and extrusion through pathways involving IL-1 and nitric oxide synthase (iNOS) (6). The molecular mechanisms through which B. pertussis exerts these effects and by which h...

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