BALF editome profiling reveals A-to-I RNA editing associated with severity and complications of Mycoplasma pneumoniae pneumonia in children

ABSTRACT Mycoplasma pneumoniae is an important human respiratory pathogen that causes mild-to-moderate community-acquired M. pneumoniae pneumonia (MPP), particularly in children. RNA editing plays a vital role in pathogen infection and host immune response, but it remains largely unknown how it coul...

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Main Authors: Yun-Yun Jin, Yun Guo, Su-Wan Xiong, Na Zhang, Jian-Huan Chen, Feng Liu
Format: Article
Language:English
Published: American Society for Microbiology 2025-03-01
Series:mSphere
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Online Access:https://journals.asm.org/doi/10.1128/msphere.01012-24
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author Yun-Yun Jin
Yun Guo
Su-Wan Xiong
Na Zhang
Jian-Huan Chen
Feng Liu
author_facet Yun-Yun Jin
Yun Guo
Su-Wan Xiong
Na Zhang
Jian-Huan Chen
Feng Liu
author_sort Yun-Yun Jin
collection DOAJ
description ABSTRACT Mycoplasma pneumoniae is an important human respiratory pathogen that causes mild-to-moderate community-acquired M. pneumoniae pneumonia (MPP), particularly in children. RNA editing plays a vital role in pathogen infection and host immune response, but it remains largely unknown how it could be involved in the epigenetic regulation of host response to M. pneumoniae infection. In the present study, we performed an epitranscriptomic analysis of adenosine to inosine (A-to-I) editing in 39 bronchoalveolar lavage fluid (BALF) samples from the severe side (SS) and the opposite side (OS) of patients with MPP. Our editome profiling identified 87 differential RNA editing (DRE) events in 50 genes, especially missense editing events that recoded C-C motif chemokine receptor-like 2 (CCRL2, p.K147R) and cyclin I (CCNI, p.R75G). The expression of adenosine deaminase acting on RNA (ADAR) significantly increased on SS compared to OS and positively correlated with the average RNA editing level and individual DRE events. Meanwhile, functional enrichment analysis showed that DRE was observed in genes primarily associated with the negative regulation of innate immune response, type I interferon production, and cytokine production. Further comparison of SS between complicated MPP (CMPP) and non-complicated MPP (NCMPP) revealed RNA editing events associated with MPP complications, with a higher ADAR expression in CMPP than NCMPP. By identifying DRE events as biomarkers associated with MPP severity and complications, our editome profiling provides new insight into the potential role played by A-to-I RNA editing in modulating the host’s immune system during M. pneumoniae infection.IMPORTANCEOur research investigates how Mycoplasma pneumoniae, a common respiratory pathogen, influences how our cells modify their genetic instructions. By studying RNA editing changes in bronchoalveolar lavage fluid from patients with M. pneumoniae pneumonia, we aim to investigate how M. pneumoniae infection alters epigenetics and contributes to the disease severity and complications. Understanding such epigenetic alterations not only sheds light on the mechanisms underlying M. pneumoniae infection but also holds potential implications for developing better diagnostic tools and therapies. Ultimately, this work may facilitate the design of more targeted treatments to alleviate the impact of respiratory infections caused by the pathogen. Our findings may also offer broader insights into how microbial infections reshape immune processes, highlighting the importance of RNA editing in host-pathogen interactions.
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spelling doaj-art-31827f88dead408aa21bb2164a5f0ae82025-08-20T03:40:25ZengAmerican Society for MicrobiologymSphere2379-50422025-03-0110310.1128/msphere.01012-24BALF editome profiling reveals A-to-I RNA editing associated with severity and complications of Mycoplasma pneumoniae pneumonia in childrenYun-Yun Jin0Yun Guo1Su-Wan Xiong2Na Zhang3Jian-Huan Chen4Feng Liu5Laboratory of Genomic and Precision Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, ChinaDepartment of Respiratory Medicine & Clinical Allergy Center, Affiliated Children’s Hospital of Jiangnan University (Wuxi Children’s Hospital), Wuxi, Jiangsu, ChinaDepartment of Respiratory Medicine & Clinical Allergy Center, Affiliated Children’s Hospital of Jiangnan University (Wuxi Children’s Hospital), Wuxi, Jiangsu, ChinaLaboratory of Genomic and Precision Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, ChinaLaboratory of Genomic and Precision Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, ChinaDepartment of Respiratory Medicine, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu, ChinaABSTRACT Mycoplasma pneumoniae is an important human respiratory pathogen that causes mild-to-moderate community-acquired M. pneumoniae pneumonia (MPP), particularly in children. RNA editing plays a vital role in pathogen infection and host immune response, but it remains largely unknown how it could be involved in the epigenetic regulation of host response to M. pneumoniae infection. In the present study, we performed an epitranscriptomic analysis of adenosine to inosine (A-to-I) editing in 39 bronchoalveolar lavage fluid (BALF) samples from the severe side (SS) and the opposite side (OS) of patients with MPP. Our editome profiling identified 87 differential RNA editing (DRE) events in 50 genes, especially missense editing events that recoded C-C motif chemokine receptor-like 2 (CCRL2, p.K147R) and cyclin I (CCNI, p.R75G). The expression of adenosine deaminase acting on RNA (ADAR) significantly increased on SS compared to OS and positively correlated with the average RNA editing level and individual DRE events. Meanwhile, functional enrichment analysis showed that DRE was observed in genes primarily associated with the negative regulation of innate immune response, type I interferon production, and cytokine production. Further comparison of SS between complicated MPP (CMPP) and non-complicated MPP (NCMPP) revealed RNA editing events associated with MPP complications, with a higher ADAR expression in CMPP than NCMPP. By identifying DRE events as biomarkers associated with MPP severity and complications, our editome profiling provides new insight into the potential role played by A-to-I RNA editing in modulating the host’s immune system during M. pneumoniae infection.IMPORTANCEOur research investigates how Mycoplasma pneumoniae, a common respiratory pathogen, influences how our cells modify their genetic instructions. By studying RNA editing changes in bronchoalveolar lavage fluid from patients with M. pneumoniae pneumonia, we aim to investigate how M. pneumoniae infection alters epigenetics and contributes to the disease severity and complications. Understanding such epigenetic alterations not only sheds light on the mechanisms underlying M. pneumoniae infection but also holds potential implications for developing better diagnostic tools and therapies. Ultimately, this work may facilitate the design of more targeted treatments to alleviate the impact of respiratory infections caused by the pathogen. Our findings may also offer broader insights into how microbial infections reshape immune processes, highlighting the importance of RNA editing in host-pathogen interactions.https://journals.asm.org/doi/10.1128/msphere.01012-24Mycoplasma pneumoniae pneumoniaA-to-I RNA editomeADARepitranscriptomicimmune response
spellingShingle Yun-Yun Jin
Yun Guo
Su-Wan Xiong
Na Zhang
Jian-Huan Chen
Feng Liu
BALF editome profiling reveals A-to-I RNA editing associated with severity and complications of Mycoplasma pneumoniae pneumonia in children
mSphere
Mycoplasma pneumoniae pneumonia
A-to-I RNA editome
ADAR
epitranscriptomic
immune response
title BALF editome profiling reveals A-to-I RNA editing associated with severity and complications of Mycoplasma pneumoniae pneumonia in children
title_full BALF editome profiling reveals A-to-I RNA editing associated with severity and complications of Mycoplasma pneumoniae pneumonia in children
title_fullStr BALF editome profiling reveals A-to-I RNA editing associated with severity and complications of Mycoplasma pneumoniae pneumonia in children
title_full_unstemmed BALF editome profiling reveals A-to-I RNA editing associated with severity and complications of Mycoplasma pneumoniae pneumonia in children
title_short BALF editome profiling reveals A-to-I RNA editing associated with severity and complications of Mycoplasma pneumoniae pneumonia in children
title_sort balf editome profiling reveals a to i rna editing associated with severity and complications of mycoplasma pneumoniae pneumonia in children
topic Mycoplasma pneumoniae pneumonia
A-to-I RNA editome
ADAR
epitranscriptomic
immune response
url https://journals.asm.org/doi/10.1128/msphere.01012-24
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