Transcriptome-wide assessment of N6-methyladenosine modification identifies different gene expression and infection-associated pathways in Treponema pallidum-infected macrophage

Zhijia Li; Litian Zhang; Yinbo Jiang; Xiaoxin Lin; Yuhui Liao; Bin Yang; Muzhou Teng

doi:10.1016/j.jdermsci.2023.02.004

Transcriptome-wide assessment of N6-methyladenosine modification identifies different gene expression and infection-associated pathways in Treponema pallidum-infected macrophage

J Dermatol Sci. 2023 Mar;109(3):108-116. doi: 10.1016/j.jdermsci.2023.02.004. Epub 2023 Feb 19.

Authors

Zhijia Li¹, Litian Zhang¹, Yinbo Jiang¹, Xiaoxin Lin¹, Yuhui Liao¹, Bin Yang², Muzhou Teng³

Affiliations

¹ Dermatology Hospital, Southern Medical University, Guangzhou, China.
² Dermatology Hospital, Southern Medical University, Guangzhou, China. Electronic address: yangbin1@smu.edu.cn.
³ Dermatology Hospital, Southern Medical University, Guangzhou, China; Lanzhou University Second Hospital, Lanzhou, China; The Second Clinical Medical College, Lanzhou University, Lanzhou, China. Electronic address: smutmz@126.com.

PMID: 36841722
DOI: 10.1016/j.jdermsci.2023.02.004

Abstract

Background: Treponema pallidum (Tp) is a widespread and destructive pathogen that leads to syphilis. As the acknowledged executor of host immunity, macrophage plays vital roles in combating the invasion and migration of Tp. However, the mechanisms of these processes are largely unknown, especially the critical driver genes and associated modifications.

Objective: We aimed to systematically dissect the global N6-methyladenosine (m⁶A) RNA modification patterns in Tp-infected macrophages.

Methods: The RNA of Tp-infected/non-infected macrophage was extracted, followed by mRNA sequencing and methylated RNA immunoprecipitation (MeRIP) sequencing. Bioinformatics analysis was executed by m⁶A peaks and motifs identification, Gene ontology and signaling pathways analysis of differentially expressed genes, and comprehensive comparison. The m⁶A levels were measured by RNA Methylation Assay, and m⁶A modified genes were determined by qPCR.

Results: Totally, 2623 unique and 3509 common m⁶A peaks were proved along with related transcripts in Tp-infected macrophages. The common m⁶A-related genes were enriched in the signals of oxidative stress, cell differentiation, and angiogenesis, while unique genes in those of metabolism, inflammation, and infection. And differentially expressed transcripts revealed various biological processes and pathways associated with catabolic and infection. They also experienced comprehensive analysis due to hyper-/hypo-methylation. And the m⁶A level of macrophage was elevated, along with qPCR validation of specific genes.

Conclusion: With a particular m⁶A transcriptome-wide map, our study provides unprecedented insights into the RNA modification of macrophage stimulated by Tp in vitro, which partially differs from other infections and may provide clues to explore the immune process for syphilis.

Keywords: Infection-associated pathways; Macrophage; MeRIP-seq; N6-methyladenosine modification; RNA-seq; Treponema pallidum.

MeSH terms

Adenosine
Humans
Macrophages
Syphilis* / genetics
Transcriptome
Treponema pallidum* / genetics

Substances

Adenosine