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

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
• cell-free DNA
• citrullinated histone H3
• MP pneumonia
• myeloperoxidase
• neutrophil extracellular traps
• NLRP3 inflammasome

Acknowledgements

The authors thank the National Natural Science Foundation of Tianjin (18JCQNJC13400), and the science foundation of Tianjin Municipal Health Bureau (No.2021092; No.2021094) for their great supports in financing this research.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Lei Yang performed the flow cytometry analysis, involved in the acquisition and analysis of clinic data. Zhihua Wang devised the experimental design. Cen Zhang wrote the paper. Yan Liu was responsible for the enrolment of patients with Mycoplasma pneumoniae pneumonia and healthy control subjects. Huijing Bao went in for designing and detecting the flow cytometry.

Additional information

Funding

The work was supported by the Science Foundation of Tianjin Municipality [18JCQNJC13400, Lei Yang], and the science foundation of Tianjin Municipal Health Bureau [No. 2023093, Zhihua Wang; No. 2021094, Cen Zhang].