Effects on the ciliated epithelium of protein D-producing and -nonproducing nontypeable Haemophilus influenzae in nasopharyngeal tissue cultures

A pair of isogenic, nontypeable Haemophilus influenzae strains, one expressing protein D and the other protein D-negative, was compared in their ability to cause damage in a human nasopharyngeal tissue culture model. Damage was assessed by measuring the ciliary beat frequency (CBF) of tissue specimens at 12 h intervals. Cultures inoculated with H. influenzae manifested a decrease in CBF beginning after 12 h, with a maximum decrease after 36 h. The impairment of ciliary function by the protein D-expressing strain was significantly greater than that caused by the protein D-negative mutant (P<.01). Tissue specimens examined by scanning and transmission electron microscopy after 24 h appeared normal. After 48 h of incubation, the protein D-expressing strain caused a significant loss of cilia. These findings suggest that protein D is involved in the pathogenesis of upper respiratory tract infections due to nontypeable H. influenzae, probably by enhancing functional and morphological damage to cilia.