Pathogenesis of IgA1 Protease-Producing and -Nonproducing Haemophilus Influenzae in Human Nasopharyngeal Organ Cultures

J Infect Dis. 1986 Nov;154(5):752-9. doi: 10.1093/infdis/154.5.752.

Abstract

We evaluated mucosal attachment, colonization, and invasion by Haemophilus influenzae in an experimental model of human nasopharyngeal tissue in organ culture. Nonpiliated, encapsulated, and nonencapsulated, IgA1 protease-deficient mutants of H. influenzae were compared with their isogenic IgA1 protease-producing parents. Damage to peripheral ciliary activity was first noted 6 hr after infection and was associated with sloughing of ciliated cells to which H. influenzae were not attached. Infection of organ cultures with each strain resulted in similar degrees and rates of ciliary damage. H. influenzae attached selectively to nonciliated epithelial cells or was associated with surface mucus. Later, disruption of epithelial tight junctions was observed, and clusters of H. influenzae were found between epithelial cells. Organisms were also seen within phagocytic vacuoles of mononuclear cells located above and below the basement membrane. In summary, encapsulated and nonencapsulated H. influenzae damaged the ciliary function of human nasopharyngeal organ cultures, attached to the mucosal surface, and invaded the epithelium. H. influenzae IgA1 protease, however, was not essential for the pathogenic steps observed in this human nasopharyngeal organ culture model.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Haemophilus Infections / enzymology
  • Haemophilus Infections / pathology
  • Haemophilus influenzae / enzymology
  • Haemophilus influenzae / pathogenicity*
  • Humans
  • Microscopy, Electron
  • Microscopy, Electron, Scanning
  • Nasopharynx / microbiology*
  • Organ Culture Techniques
  • Peptide Hydrolases / biosynthesis*
  • Serine Endopeptidases*
  • Time Factors

Substances

  • Peptide Hydrolases
  • Serine Endopeptidases
  • IgA-specific serine endopeptidase