Myeloid Sirtuin 2 Expression Does Not Impact Long-Term Mycobacterium tuberculosis Control.

Area of Science:

• Immunology
• Microbiology
• Molecular Biology

Background:

• Sirtuins (Sirts) are enzymes regulating cellular processes via deacetylation.
• Sirtuin 2 (Sirt2) is known to inhibit inflammation and aid acute Listeria monocytogenes infection.
• The role of Sirt2 in chronic infections, like tuberculosis, is not well understood.

Purpose of the Study:

• To investigate the impact of myeloid-specific Sirtuin 2 (Sirt2) deletion on Mycobacterium tuberculosis infection.
• To determine if Sirt2 plays a role in the host's response to chronic tuberculosis.

Main Methods:

• Utilized conditional mice with Sirt2 specifically deleted in myeloid lineage.
• Infected mice with Mycobacterium tuberculosis and assessed bacterial load in lungs and liver at various time points (days 60 and 120).
• Analyzed inflammatory cell infiltration and transcription levels of key immune-related genes (IFN-γ, IL-17, TNF, IL-6, NOS2) in the lungs.

Main Results:

• Myeloid-specific Sirt2 deletion led to a transient increase in Mycobacterium tuberculosis bacterial load in the lungs and liver.
• No significant differences in bacterial burden were observed in the long-term infection (days 60 and 120).
• The initial increase in bacterial growth was not attributed to altered inflammatory cell infiltration or key cytokine/chemokine expression.

Conclusions:

• Sirtuin 2 (Sirt2) expression has a temporary effect on Mycobacterium tuberculosis infection dynamics.
• Modulating Sirt2 activity in vivo is unlikely to influence the outcome of chronic tuberculosis infections.
• These findings suggest Sirt2 is not a primary target for treating chronic M. tuberculosis infections.