Single-cell transcriptomic profiles reveal changes associated with BCG-induced trained immunity and protective...

Area of Science:

• Immunology
• Vaccinology
• Systems Biology

Background:

• Bacillus Calmette-Guérin (BCG) vaccine provides protection against tuberculosis.
• BCG also confers non-specific protection against other infections via trained immunity.
• Understanding BCG-induced immune reprogramming is crucial for harnessing its broader benefits.

Purpose of the Study:

• To investigate BCG-induced immune reprogramming at the single-cell level.
• To identify genes and molecular pathways involved in BCG-mediated trained immunity.
• To link in vivo BCG administration to transcriptomic changes and validated genetic findings.

Main Methods:

• Single-cell transcriptomic measurements before and after BCG vaccination.
• Secondary immune stimulation with bacterial lipopolysaccharide (LPS).
• Co-expression network analysis and in vitro validation of humanin isoforms.

Main Results:

• BCG vaccination alters LPS-induced immune responses, reducing systemic inflammation.
• Identified 75 genes with modified LPS responses, including heightened CCL3 and CCL4 expression.
• Observed altered gene module coordination, with some losing and others gaining coordination, including humanin isoforms inducing trained immunity.

Conclusions:

• BCG administration leads to significant single-cell transcriptomic changes.
• Specific gene modules and humanin isoforms are implicated in BCG-induced trained immunity.
• Findings provide insights into the molecular mechanisms underlying BCG's non-specific protective effects.