Analysis of Inflammatory and Homeostatic Roles of Tissue-resident Macrophages in the Progression of Cholesteatoma by RNA-Seq

ABSTRACT

Background

Tissue-resident macrophages (TRMØs) can act as innate-immune sentinels to protect body against microbe invaders and stimulating materials such as cholesterol crystals in cholesteatoma, as well as to preserve tissue integrity by cleaning unwanted cellular debris.

Methods

TRMØs in the incised middle ear tissues were obtained from the patients with cholesteatoma as an experimental group and the patients without cholesteatoma as a control group. Differential gene expression profiling of TRMØs was conducted between two groups by analyzing GO processes, KEGG and GSEA pathways of inflammation, tissue repair and homeostasis.

Results

The current study showed that 145 of 7060 genes were significantly up-regulated (logFC>2 and FDR <0.05) when compared with the patients without cholesteatoma. GO process, GSEA and Cytoscape analysis of the over-expressed genes illustrated the boosted inflammatory and anti-infection functions of TRMØs existed neutrophil function, leukocyte migration, and adaptive immune response involved receptors and signaling pathways. Whereas the homeostasis and repair functions of TRMØs were affected from up-regulated genes, such as over-expressed keratin-13 that helped form the outer keratinising squamous epithelial layer, and over-expressed MMPs that activated the extracellular matrix molecules to promote inflammation and disturb tissue remodeling. Additionally, 74 down-regulated genes (logFC<-2 and FDR <0.05) also affected the homeostasis and repair functions by affecting extracelluar matrix structure and contractile fibres in TRMØs.

Conclusions

The cellular and molecular levels in cholesteatoma is attributable to chronic infection and several disturbed cellular biological processes involving cell integrity and tissue remodeling.

KEYWORDS:

• Middle ear
• cholesteatoma
• tissue-resident macrophages (TRMØ)
• RNA-Seq
• gene expression

Highlights

1. Among 7060 genes, 145 genes were up-regulated in the patients with cholesteatoma, contributing to boosted inflammatory and anti-infection functions, including B cell and T cell immunity, and neutrophil function.

2. The homeostasis and repair functions of TRMØs are affected both from up-regulated genes, such as over-expressed keratin-13 and MMPs, as well as down-regulated genes that are responsible for extracelluar matrix structure and contractile fibres.

Disclosure statement

No potential conflict of interest relevant to this article was reported.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This study was supported by the Natural Science Foundation of Zhejiang Province, China (No. LY16H130001) and the Wenzhou basic scientific research project (No. 2018Y0213).