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Macrophage responses to CF pathogens: JNK MAP kinase signaling by Burkholderia cepacia complex lipopolysaccharide

Suzanne McKeon1, Siobhán McClean, Máire Callaghan

  • 1Centre of Microbial Host Interactions, ITT-Dublin, Dublin, Ireland.

FEMS Immunology and Medical Microbiology
|July 7, 2010
PubMed

Insights

Burkholderia cepacia complex (Bcc) bacteria, especially Burkholderia multivorans, are more readily internalized by macrophages and provoke a stronger inflammatory response in cystic fibrosis (CF) patients than other common pathogens. This highlights Bcc

Area of Science:

  • Immunology
  • Microbiology
  • Pulmonology

Background:

  • Chronic bacterial lung infections are a major cause of mortality in cystic fibrosis (CF).
  • Burkholderia cepacia complex (Bcc) bacteria, particularly Burkholderia multivorans, are increasingly prevalent and challenging pathogens in CF patients.
  • Bcc infections can lead to severe pneumonia and rapid lung function decline.

Purpose of the Study:

  • To compare the host immune response, specifically macrophage behavior, to different Bcc species and common CF pathogens.
  • To elucidate the mechanisms by which Bcc species, particularly B. multivorans, interact with and activate immune cells.

Main Methods:

  • U937 macrophage cell line was used to model the host immune response.
  • Macrophage internalization rates of Bcc species (B. cenocepacia, B. multivorans) were compared to Pseudomonas aeruginosa and Staphylococcus aureus.
  • Pro-inflammatory cytokine production (TNF-α, IL-1β) by macrophages was measured.
  • The role of lipopolysaccharide (LPS) from B. multivorans in activating macrophages and downstream signaling pathways (JNK MAPK) was investigated.

Main Results:

  • Bcc strains, B. cenocepacia and B. multivorans, showed significantly higher internalization by U937 macrophages compared to P. aeruginosa and S. aureus.
  • Both Bcc strains induced greater levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) from macrophages than P. aeruginosa.
  • Lipopolysaccharide (LPS) from B. multivorans was identified as a potent inducer of pro-inflammatory cytokines.
  • B. multivorans LPS primarily signaled through the c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathway.

Conclusions:

  • Bcc organisms, especially B. multivorans, exhibit enhanced interaction with and activation of macrophages compared to other common CF pathogens.
  • The lipopolysaccharide component of B. multivorans plays a critical role in driving the pro-inflammatory macrophage response via the JNK MAPK pathway.
  • These findings contribute to understanding the pathogenesis of Bcc infections in CF and may inform therapeutic strategies.

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