Lipooligosaccharide-independent alteration of cellular homeostasis in Neisseria meningitidis-infected epithelial cells

Robert A. Bonnah, Jenny Hoelter, Liana Steeghs, Caroline A. Enns, Magdalene "Maggie" So, Martina U. Muckenthaler

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Neisseria meningitidis (MC) is an important cause of meningitis and septic shock. Primary loose attachment of MC to host epithelial cells is mediated by type IV pili. Lipooligosaccharide (LOS), opacity (Opa) proteins and glycolipid adhesins facilitate subsequent tight attachment. MC infection causes numerous changes in host epithelial cell homeostasis. These include cortical plaque formation, increased expression of proinflammatory cytokines and alterations in host iron homeostasis. Using both biochemical and genetic approaches, we examined the role of LOS in mediating these events. We first examined specific cellular iron homeostasis changes that occur following addition of purified MC LOS to epithelial cells. Using an MC mutant that completely lacks LOS (MC lps tbp), we examined pili-mediated attachment and cortical plaque formation in human endocervical epithelial cells (A431). We also tested whether the lack of LOS alters cellular homeostasis, including changes in the levels of host stress response factors and proinflammatory cytokines. MC lps tbp elicited the formation of cortical plaques in A431 cells. However, the plaques were less pronounced than those formed by the MC parent. Surprisingly, the proinflammatory cytokine TNFα was upregulated during infection in MC lps tbp-infected cells. Furthermore, alterations in iron homeostasis, including lower transferrin receptor 1 (TfR-1) levels, altered TfR-1 trafficking, an 'iron-starvation' gene expression profile and low iron regulatory protein (IRP) binding activity are independent of LOS. Our results demonstrate that LOS is partially involved in both the attachment to host cells and formation of cortical plaques. However, TNFα induction and changes in iron homeostasis observed in MC-infected epithelial cells are independent of LOS.

Original languageEnglish (US)
Pages (from-to)869-885
Number of pages17
JournalCellular Microbiology
Volume7
Issue number6
DOIs
StatePublished - Jun 2005
Externally publishedYes

Fingerprint

Neisseria meningitidis
Homeostasis
Epithelial Cells
Iron
Transferrin Receptors
Cytokines
Iron-Regulatory Proteins
lipid-linked oligosaccharides
Glycolipids
Septic Shock
Starvation
Infection
Transcriptome
Meningitis
Protein Binding
Gene expression
Molecular Biology

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Microbiology

Cite this

Lipooligosaccharide-independent alteration of cellular homeostasis in Neisseria meningitidis-infected epithelial cells. / Bonnah, Robert A.; Hoelter, Jenny; Steeghs, Liana; Enns, Caroline A.; So, Magdalene "Maggie"; Muckenthaler, Martina U.

In: Cellular Microbiology, Vol. 7, No. 6, 06.2005, p. 869-885.

Research output: Contribution to journalArticle

Bonnah, Robert A. ; Hoelter, Jenny ; Steeghs, Liana ; Enns, Caroline A. ; So, Magdalene "Maggie" ; Muckenthaler, Martina U. / Lipooligosaccharide-independent alteration of cellular homeostasis in Neisseria meningitidis-infected epithelial cells. In: Cellular Microbiology. 2005 ; Vol. 7, No. 6. pp. 869-885.
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