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Penicillin binding proteins as danger signals: meningococcal penicillin binding protein 2 activates dendritic cells

Marcelo Hill1, Ala-Eddine Deghmane, Mercedes Segovia

  • 1INSERM U643, Nantes, CHU de Nantes, IUN, Nantes, Université de Nantes, UMR 643, Nantes, France.

Plos One
|November 3, 2011
PubMed

Insights

Meningococcal PBP2 protein activates human dendritic cells (DCs), enhancing immune responses. This novel function as a pathogen-associated molecular pattern (PAMP) involves TLR4 binding and NF-kB activation, crucial for host defense.

Area of Science:

  • Immunology
  • Microbiology
  • Cell Biology

Background:

  • Neisseria meningitidis is a pathogen causing severe diseases.
  • Meningococcal penicillin-binding proteins (PBPs), especially PBP2, are linked to antibiotic resistance.

Purpose of the Study:

  • To investigate a novel function of meningococcal PBP2 beyond its role in bacterial resistance.
  • To determine if PBP2 influences dendritic cell (DC) maturation and immune activation.

Main Methods:

  • Assessing DC maturation markers (MHC II, CD80, CD86) upon PBP2 treatment.
  • Utilizing anti-PBP2 antibodies and TLR4 blocking experiments to confirm PBP2's role.
  • Investigating mechanistic pathways including NF-kB activation and TLR4 binding via immunoprecipitation.

Main Results:

  • PBP2 dose-dependently activated human and mouse DCs, upregulating MHC II, CD80, and CD86.
  • PBP2-induced DC maturation was abolished by anti-PBP2 antibodies and required TLR4 expression.
  • PBP2 induced p65 NF-kB nuclear localization and directly bound to TLR4, independent of endotoxin contamination.

Conclusions:

  • Meningococcal PBP2 acts as a novel pathogen-associated molecular pattern (PAMP).
  • PBP2 binding to TLR4 triggers DC maturation and immune responses.
  • This interaction is a critical host-pathogen interface mechanism for initiating immune defense.

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