Single-cell transcriptome analysis reveals the dysregulated monocyte state associated with tuberculosis progression

Area of Science:

• Immunology
• Genomics
• Infectious Diseases

Background:

• Monocytes are key regulators of immune balance in tuberculosis (TB).
• Understanding monocyte subset roles in TB immunity is crucial for developing new therapies.

Purpose of the Study:

• To investigate the roles of monocyte subsets in TB progression using single-cell RNA sequencing.
• To identify key genes, transcription factors, and signaling pathways involved in TB pathogenesis.

Main Methods:

• Retrieved and processed single-cell RNA-seq data (SRP247583).
• Employed bioinformatics analysis, including pseudotime and cell communication analysis.
• Investigated transcription factor regulatory networks and ferroptosis-associated genes.

Main Results:

• Classical monocytes increased, while non-classical monocytes decreased with TB progression.
• Identified an abnormal monocyte differentiation trajectory and key genes (CEBPB, CORO1A).
• Found IRF9 downregulation in non-classical monocytes, potentially impairing ferroptosis and identified MEF2C, MICU1, PRR5 as targets. MIF and LGALS9 highlighted in cell communication.

Conclusions:

• Single-cell sequencing and bioinformatics reveal critical roles of monocyte subsets in TB infection.
• Findings provide insights into TB pathogenesis and potential therapeutic targets.