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Elicitation of epithelial cell-derived immune effectors by outer membrane vesicles of nontypeable Haemophilus influenzae.

Publication ,  Journal Article
Sharpe, SW; Kuehn, MJ; Mason, KM
Published in: Infect Immun
November 2011

Outer membrane vesicles (OMVs) are produced by all Gram-negative microorganisms studied to date. The contributions of OMVs to biological processes are diverse and include mediation of bacterial stress responses, selective packaging and secretion of virulence determinants, modulation of the host immune response, and contributions to biofilm formation and stability. First characterized as transformasomes in Haemophilus, these membranous blebs facilitate transfer of DNA among bacteria. Nontypeable Haemophilus influenzae (NTHI), an opportunistic pathogen of the upper and lower respiratory tracts, produces OMVs in vivo, but there is a paucity of information regarding both the composition and role of OMVs during NTHI colonization and pathogenesis. We demonstrated that purified NTHI vesicles are 20 to 200 nm in diameter and contain DNA, adhesin P5, IgA endopeptidase, serine protease, and heme utilization protein, suggesting a multifaceted role in virulence. NTHI OMVs can bind to human pharyngeal epithelial cells, resulting in a time- and temperature-dependent aggregation on the host cell surface, with subsequent internalization. OMVs colocalize with the endocytosis protein caveolin, indicating that internalization is mediated by caveolae, which are cholesterol-rich lipid raft domains. Upon interaction with epithelial cells, NTHI OMVs stimulate significant release of the immunomodulatory cytokine interleukin-8 (IL-8) as well as the antimicrobial peptide LL-37. Thus, we demonstrated that NTHI OMVs contain virulence-associated proteins that dynamically interact with and invade host epithelial cells. Beyond their ability to mediate DNA transfer in Haemophilus, OMV stimulation of host immunomodulatory cytokine and antimicrobial peptide release supports a dynamic role for vesiculation in NTHI pathogenesis and clinically relevant disease progression.

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Published In

Infect Immun

DOI

EISSN

1098-5522

Publication Date

November 2011

Volume

79

Issue

11

Start / End Page

4361 / 4369

Location

United States

Related Subject Headings

  • Virulence
  • Microbiology
  • Lipopolysaccharides
  • Interleukin-8
  • Humans
  • Haemophilus influenzae
  • Epithelial Cells
  • DNA, Bacterial
  • Cell Membrane
  • Cell Line
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Sharpe, S. W., Kuehn, M. J., & Mason, K. M. (2011). Elicitation of epithelial cell-derived immune effectors by outer membrane vesicles of nontypeable Haemophilus influenzae. Infect Immun, 79(11), 4361–4369. https://doi.org/10.1128/IAI.05332-11
Sharpe, Samantha W., Meta J. Kuehn, and Kevin M. Mason. “Elicitation of epithelial cell-derived immune effectors by outer membrane vesicles of nontypeable Haemophilus influenzae.Infect Immun 79, no. 11 (November 2011): 4361–69. https://doi.org/10.1128/IAI.05332-11.
Sharpe, Samantha W., et al. “Elicitation of epithelial cell-derived immune effectors by outer membrane vesicles of nontypeable Haemophilus influenzae.Infect Immun, vol. 79, no. 11, Nov. 2011, pp. 4361–69. Pubmed, doi:10.1128/IAI.05332-11.

Published In

Infect Immun

DOI

EISSN

1098-5522

Publication Date

November 2011

Volume

79

Issue

11

Start / End Page

4361 / 4369

Location

United States

Related Subject Headings

  • Virulence
  • Microbiology
  • Lipopolysaccharides
  • Interleukin-8
  • Humans
  • Haemophilus influenzae
  • Epithelial Cells
  • DNA, Bacterial
  • Cell Membrane
  • Cell Line