The Therapeutic Potential of Neutrophil Extracellular Traps and NLRP3 Inflammasomes in Mycoplasma pneumoniae Pneumonia

Immunol Invest. 2024 Aug;53(6):975-988. doi: 10.1080/08820139.2024.2364796. Epub 2024 Jun 14.

Abstract

Introduction: Mycoplasma pneumoniae (MP) is the most common pathogen of community-acquired pneumonia in children. However, the role of neutrophil extracellular traps (NETs) in the pathogenesis of MP is unclear.

Methods: Both the level of NETs were detected between the 60 MP pneumonia patients and 20 healthy controls, whose the clinical characteristics were compared. Additionally, NETs formation induced by community-acquired respiratory distress syndrome (CARDS) toxin was also analyzed through transcriptome sequencing.

Results: The levels of cell-free DNA, Cit-H3, and MPO-DNA complexes were significantly increased in the patients with MP pneumonia. Importantly, both cell-free DNA and LDH were higher in hospitalized patients with severity than those without severity. In addition, CARDS toxin induced the NETs formation in vitro and in vivo. Transcriptomics GO and KEGG pathway analysis indicate that NOD like receptor signaling pathway and Toll-like receptor signaling pathway are significantly enriched. Finally, we found that DNase I significantly attenuated the higher levels of Cit-H3, and up-regulation of interleukin-1β (IL-1β) and interleukin-18 (IL-18) by down-regulating the expression of NLRP3 and Caspase1(p20) in the lung tissues.

Discussion: These results indicate that inhibiting excessive activation of NLRP3 inflammasomes, and NETs formation may alleviate MP pneumonia.

Keywords: Caspase1; MP pneumonia; NLRP3 inflammasome; cell-free DNA; citrullinated histone H3; myeloperoxidase; neutrophil extracellular traps.

MeSH terms

  • Animals
  • Bacterial Proteins / metabolism
  • Bacterial Toxins
  • Cell-Free Nucleic Acids
  • Child
  • Deoxyribonuclease I / metabolism
  • Extracellular Traps* / immunology
  • Extracellular Traps* / metabolism
  • Female
  • Humans
  • Inflammasomes* / immunology
  • Inflammasomes* / metabolism
  • Interleukin-18 / metabolism
  • Interleukin-1beta / metabolism
  • Male
  • Mice
  • Mycoplasma pneumoniae* / immunology
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Pneumonia, Mycoplasma* / immunology
  • Pneumonia, Mycoplasma* / metabolism
  • Signal Transduction

Substances

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Inflammasomes
  • NLRP3 protein, human
  • CARDS toxin, Mycoplasma pneumoniae
  • Bacterial Proteins
  • Cell-Free Nucleic Acids
  • Deoxyribonuclease I
  • Interleukin-18
  • Interleukin-1beta
  • Bacterial Toxins