Analysis of damage to human ciliated nasopharyngeal epithelium by Neisseria meningitidis

Abstract

We used an in vitro model of human nasopharyngeal tissue in organ culture to evaluate the effects of Neisseria meningitidis on human cilia and ciliary function. Encapsulated, viable meningococci damaged ciliated epithelium of nasopharyngeal organ cultures, whereas Neisseria subflava, a commensal species, did not. Meningococcus-induced ciliary damage was due to loss of ciliated cells to which meningococci were not attached. Damage was seen with piliated and nonpiliated meningococci and did not appear to require the presence of other specific meningococcal surface proteins. Meningococcal viability was a requirement for both ciliary damage and interactions of meningococci with microvilli of nonciliated epithelial cells. That is, filter-sterilized supernatants from meningococcus-infected organ cultures, heat-killed meningococci at high inoculum, and purified meningococcal or gonococcal lipopolysaccharide at concentrations of 100 Fg/ml did not damage ciliary activity of nasopharyngeal organ cultures. In contrast, meningococcal lipopolysaccharide at 10 ,ug/mI markedly damaged ciliary activity of human fallopian tube organ cultures, suggesting a selective toxicity of lipopolysaccharide for specific human ciliated cells. Damage to nasopharyngeal ciliated epithelium by N. meningitidis may be an important first step in meningococcal colonization of the human nasopharynx, but meningococcal lipopolysaccharide does not appear to be directly responsible for this toxicity.

Stable expression of lipooligosaccharide antigens during attachment, internalization, and intracellular processing of Neisseria gonorrhoeae in infected epithelial cells

“…The latter is of interest since LOS might give rise, because of its partially hydrophobic nature, to nonspecific lipid-lipid interactions. A specific interaction of gonococcal LOS and host cells previously has been found with respect to the toxic effect of LOS on ciliated epithelial cells (19). This toxicity shows a remarkable host and tissue specificity and is related to the LOS binding capacity of the various host cells (5).…”

“…The significance of LOS and its variability in the pathogenesis of Neisseria infections at the level of the mucous membrane is much less evident. Purified LOS of Neisseria meningitidis and N. gonorrhoeae damage the ciliary activity in the human fallopian tube organ culture model, but this toxic effect was not found in the nasopharyngeal infection model (19). In fact, the role of LOS as a virulence determinant at the primary site of neisserial infections (nasopharynx, urethra, cervix, and conjunctiva) is still obscure.…”

Evaluation of the chick embryo for the determination of relative virulence ofNeisseria meningitidis

“…Because low numbers of infecting bacteria (500 to 5000 CFU) are required to elicit virulence differences, it seems possible that the differential virulence observed at this age of the embryo, and not earlier, is the result of differences in the phagocytic ability of the host. Since the inoculum was injected into the yolk, it is possible that the mutant was less susceptible to phagocytosis than the wild-type strain, whose pili could serve as organs of attachment [20].…”

Interaction of pathogenic neisseriae with nonphagocytic cells.

“…Shortly after colonization, neighboring uncolonized ciliated cells stop beating and slough from the tissue. Bacterial lipooligosaccharide (LOS) and cell wall peptidoglycan are strongly implicated in GC-mediated toxicity (36,37,70,71), and there is also evidence that MC LOS has a toxic activity, but only on human fallopian tube organ culture and not human pharyngeal organ culture, suggesting a selective toxicity (115). These studies with tissue segments strongly suggest that bacteria enter the apical side of the epithelial cells, transcytose to and exocytose through the basolateral side of the cells, and enter the subepithelial matrix.…”