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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| Language: | English |
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American Society for Microbiology
2025-03-01
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| 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. |
| format | Article |
| id | doaj-art-31827f88dead408aa21bb2164a5f0ae8 |
| institution | Kabale University |
| issn | 2379-5042 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| 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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