Noncanonical Differentiation of Memory B Cells Drives Latent Tuberculosis Infection Reactivation Upon Tumor Necrosis...

Area of Science:

• Immunology
• Genomics
• Computational Biology

Background:

• Tumor necrosis factor inhibitors (TNFi) are crucial for autoimmune disease treatment.
• Latent tuberculosis infection (LTBI) reactivation is a significant risk associated with TNFi therapy.
• The precise mechanisms driving TNFi-associated LTBI reactivation remain unclear.

Purpose of the Study:

• To investigate the transcriptomic landscape of memory B cells during tuberculosis progression and TNFi therapy.
• To elucidate the molecular mechanisms underlying LTBI reactivation in patients treated with TNFi.
• To identify potential biomarkers and therapeutic targets for preventing TNFi-associated tuberculosis.

Main Methods:

• Integrated analysis of six transcriptomic datasets.
• Utilized pathway enrichment, pseudotime, and transcription factor analyses.
• Employed bioinformatics and single-cell RNA sequencing approaches.

Main Results:

• Identified distinct transcriptional profiles in memory B cells during active tuberculosis (ATB) and TNFi treatment.
• Discovered a ROR1+ memory B cell subtype with downregulated B cell genes and suppressed immune pathways.
• Observed metabolic reprogramming, including enhanced oxidative phosphorylation, in memory B cells, potentially disrupting immune balance and increasing tuberculosis susceptibility.

Conclusions:

• Memory B cells play a critical role in active tuberculosis progression and response to TNFi therapy.
• Metabolic alterations in memory B cells may be a key factor in LTBI reactivation following TNFi treatment.
• The findings provide insights into TNFi-associated tuberculosis susceptibility and suggest novel therapeutic strategies targeting memory B cell metabolism.