Role of a fluid-phase PRR in fighting an intracellular pathogen: PTX3 in Shigella infection

Valeria Ciancarella1, Luigi Lembo-Fazio1, Ida Paciello1

  • 1Department of Biology and Biotechnology "Charles Darwin", Sapienza-Università di Roma, Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Roma, Italy.

Plos Pathogens
|December 12, 2018
PubMed

Insights

Pentraxin 3 (PTX3) shows antibacterial activity against Shigella, protecting mice from infection. Elevated PTX3 levels in patients correlate with shigellosis severity, suggesting its potential as a therapeutic and diagnostic marker.

Area of Science:

  • Immunology
  • Microbiology
  • Infectious Diseases

Background:

  • Shigella spp. cause bacillary dysentery through mucosal invasion and inflammation.
  • Pentraxin 3 (PTX3), a soluble pattern recognition receptor, is a key component of innate immunity.

Purpose of the Study:

  • To investigate the role of PTX3 in Shigella pathogenesis and its potential therapeutic applications.
  • To explore PTX3 as a potential biomarker for shigellosis severity.

Main Methods:

  • In vivo studies using intranasal infection of mice with S. flexneri and treatment with recombinant PTX3.
  • In vitro assays to assess PTX3's antibacterial activity, epithelial cell invasion inhibition, and serum bactericidal activity.
  • Analysis of PTX3 production upon LPS-TLR4 stimulation.
  • Correlation analysis of plasma PTX3 levels with symptom severity in infected patients.

Main Results:

  • Recombinant PTX3 treatment rescued mice from S. flexneri infection.
  • PTX3 demonstrated in vitro antibacterial activity against Shigella, inhibited epithelial cell invasion, and enhanced serum bactericidal activity.
  • PTX3 production was induced by LPS-TLR4 stimulation, dependent on Shigella lipid A structure.
  • Plasma PTX3 levels strongly correlated with the severity of shigellosis symptoms in patients.

Conclusions:

  • PTX3 is a novel factor in Shigella pathogenesis with potential therapeutic benefits against shigellosis.
  • Plasma PTX3 levels may serve as a valuable biomarker for assessing shigellosis infection severity.

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