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Following in Real Time the Impact of Pneumococcal Virulence Factors in an Acute Mouse Pneumonia Model Using Bioluminescent Bacteria
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Myeloid-related protein-14 contributes to protective immunity in gram-negative pneumonia derived sepsis

Ahmed Achouiti1, Thomas Vogl, Constantin F Urban

  • 1Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. a.achouiti@amc.nl

Plos Pathogens
|November 8, 2012
PubMed

Insights

Myeloid related proteins MRP8/14 are crucial for fighting Klebsiella pneumoniae pneumonia. These proteins, part of neutrophil extracellular traps, exhibit antimicrobial activity essential for innate immunity and survival.

Area of Science:

  • Immunology
  • Microbiology
  • Infectious Diseases

Background:

  • Klebsiella pneumoniae causes pneumonia and sepsis.
  • Myeloid related proteins MRP8 (S100A8) and MRP14 (S100A9) are neutrophil proteins forming heterodimers.
  • MRP8/14's role in sepsis is debated, with potential contributions to organ damage.

Purpose of the Study:

  • To investigate the role of MRP8/14 in Klebsiella pneumoniae pneumonia-derived sepsis.
  • To elucidate the protective or detrimental functions of MRP8/14 in this infection model.

Main Methods:

  • Utilized a mouse model of K. pneumoniae pneumonia.
  • Compared wildtype and Mrp14-deficient (mrp14(-/-)) mice.
  • Assessed bacterial dissemination, organ damage, survival, macrophage phagocytosis, and in vitro antimicrobial activity of MRP8/14 and neutrophil extracellular traps (NETs).

Main Results:

  • K. pneumoniae infection increased MRP8/14 levels in lungs and plasma.
  • Mice lacking Mrp14 showed increased bacterial spread, organ damage, and reduced survival.
  • MRP8/14 heterodimers, but not individual proteins, inhibited K. pneumoniae growth in vitro via cation chelation.
  • NETs from wildtype neutrophils inhibited bacterial growth, an effect dependent on MRP14 and zinc.

Conclusions:

  • MRP8/14 plays a key role in protective innate immunity against K. pneumoniae pneumonia.
  • The antimicrobial activity of MRP8/14, particularly within NETs, is crucial for controlling Klebsiella infection.
  • MRP8/14 contributes to host defense rather than exacerbating sepsis in this model.

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