Probing Dermal Immunity to Mycobacteria through a Controlled Human Infection Model

Area of Science:

• Immunology
• Dermatology
• Microbiology

Background:

• Cutaneous mycobacterial infections present significant diagnostic and treatment challenges.
• Understanding the skin's immune response is key to developing novel therapies.

Purpose of the Study:

• To investigate the early systemic and local dermal immune responses to Mycobacterium bovis bacillus Calmette-Guérin (BCG) in a controlled human infection model.
• To explore cell-to-cell communication within the skin during the initial phase of infection.

Main Methods:

• Controlled human intradermal BCG (Tice strain) challenge in 10 participants, randomized to isoniazid or no treatment.
• Systemic immune profiling via flow cytometry, RNA sequencing (RNA-seq), and serum antibody assessments.
• Skin biopsy immune profiling using mass cytometry and single-cell RNA-seq at days 3 and 15 post-challenge.

Main Results:

• Systemic immune responses were detectable as early as 8 days post-challenge in BCG-naive individuals.
• Single-cell RNA-seq identified diverse immune and non-immune skin cells and inferred cell-cell communication pathways.
• Early (day 3) communication involved non-immune cells signaling to monocytes, shifting to a more balanced communication by day 15.

Conclusions:

• Non-immune cells play a significant role in the early dermal immune response to mycobacteria.
• Human challenge studies are valuable for understanding mycobacterial infections and informing therapeutic strategies.