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Neisseria gonorrhoeae-mediated inhibition of apoptotic signalling in polymorphonuclear leukocytes

Adrienne Chen1, H Steven Seifert

  • 1Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, 303 E. Chicago Avenue, S213, Chicago, IL 60611, USA.

Infection and Immunity
|August 17, 2011
PubMed

Insights

Neisseria gonorrhoeae infection inhibits polymorphonuclear leukocyte (PMN) apoptosis, prolonging cell survival. This interaction may facilitate bacterial replication and transmission.

Area of Science:

  • Immunology
  • Microbiology
  • Cell Biology

Background:

  • Neisseria gonorrhoeae (gonococcus) extensively interacts with polymorphonuclear leukocytes (PMNs) during infection.
  • PMNs are crucial innate immune cells that combat bacterial pathogens but are short-lived and undergo apoptosis.
  • Understanding gonococcal modulation of PMN apoptosis is vital for comprehending infection dynamics and potential bacterial replication sites.

Purpose of the Study:

  • To investigate the effect of Neisseria gonorrhoeae infection on PMN survival and apoptosis.
  • To determine if N. gonorrhoeae can modulate spontaneous and induced apoptosis in PMNs.
  • To validate the use of HL-60 myeloid leukemia cells as a model for N. gonorrhoeae-PMN interactions.

Main Methods:

  • Development and validation of an HL-60 cell culture model for PMN infection.
  • Infection of both HL-60 cells and primary human PMNs with N. gonorrhoeae.
  • Assessment of apoptosis induction (spontaneous and triggered by staurosporine/TRAIL) and NF-κB signaling activation.

Main Results:

  • N. gonorrhoeae infection alone did not induce apoptosis in HL-60 cells or primary PMNs.
  • N. gonorrhoeae actively inhibited spontaneous apoptosis and apoptosis induced by staurosporine (STS) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL).
  • Infection activated NF-κB signaling and induced secretion of pro-inflammatory cytokines and chemokines in both cell types.

Conclusions:

  • The HL-60 cell line effectively models Neisseria gonorrhoeae-PMN interactions.
  • N. gonorrhoeae actively inhibits multiple apoptosis pathways to prolong PMN survival.
  • Prolonged PMN survival may facilitate gonococcal survival, replication, and transmission.

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