Trained Immunity: Gut Bacteria & Bone Marrow Connection

A recently published study explores the impact of gut microbiota translocation, particularly Enterococcus faecalis, on inducing trained immunity (TI) in myeloid progenitors within the bone marrow. Key findings include:

Gut Barrier Disruption and Trained Immunity

• Dextran sulfate sodium (DSS) treatment in mice leads to gut barrier disruption, allowing E. faecalis to translocate to the bone marrow.
• This translocation triggers Mincle-mediated trained immunity in bone marrow progenitors, enhancing inflammatory responses.

Mincle Receptor’s Role

• The C-type lectin receptor Mincle (Clec4e) is critical for sensing E. faecalis and driving trained immunity.
• Mincle-deficient mice showed impaired trained immunity and reduced inflammation upon DSS treatment.

Protective vs. Detrimental Effects

• While trained immunity provides protection against secondary infections, it may exacerbate inflammation-related diseases such as colitis.
• Mincle activation can promote both beneficial immune responses and pathological inflammation.

Experimental Findings

• DSS-treated mice exhibited increased tumor necrosis factor (TNF) and interleukin-6 (IL-6) production upon pathogen challenge.
• Bone marrow progenitors showed metabolic and epigenetic reprogramming indicative of long-term immune adaptation.

Human Relevance

• E. faecalis also induced trained immunity features in human monocytes, suggesting potential clinical implications.
• The study highlights the complex interplay between gut microbiota translocation and systemic immune responses, with implications for inflammatory diseases and potential therapeutic interventions.

Citation:

Robles-Vera, I., et al. (2025). Microbiota translocation following intestinal barrier disruption promotes Mincle-mediated training of myeloid progenitors in the bone marrow. Immunity, S1074-7613(24)00577-6. Advance online publication. https://doi.org/10.1016/j.immuni.2024.12.012