Single-cell transcriptomic analysis reveals a decrease in the frequency of macrophage-RGS1^high subsets in patients...

Area of Science:

• Immunology
• Infectious Diseases
• Genomics

Background:

• Immune cell subsets play a role in Mycobacterium tuberculosis (MTB) infection.
• The specific immune cell subsets involved in osteoarticular tuberculosis (OTB) are not well understood.
• Single-cell RNA sequencing (scRNA-Seq) can elucidate immune cell phenotypes and functions.

Purpose of the Study:

• To investigate the phenotypes and functions of immune cell subsets in patients with OTB using scRNA-Seq.
• To identify potential biomarkers for OTB diagnosis and treatment monitoring.

Main Methods:

• scRNA-Seq was performed on pathological and healthy adjacent tissues from OTB patients.
• Unsupervised clustering and uniform manifold approximation and projection (UMAP) were used for cell subset identification and visualization.
• Immunohistochemistry and flow cytometry were employed to validate findings in OTB, osteoarticular bacterial infection (OBI), and healthy control (HC) samples.

Main Results:

• Thirteen distinct cell subsets were identified in OTB tissues.
• The frequency of the macrophage-RGS1^high subset was significantly decreased in OTB tissues, correlating with increased MTB susceptibility via ferroptosis.
• Decreased macrophage-RGS1^high subset frequency in OTB tissues and blood samples differentiated OTB patients from HCs and OBI patients.

Conclusions:

• The macrophage-RGS1^high subset is reduced in OTB patients and may increase with effective treatment.
• The macrophage-RGS1^high subset shows potential as a diagnostic biomarker for OTB.
• This subset could also serve as a biomarker for monitoring the efficacy of OTB treatment.