Abstract
Sirtuins (Sirts) regulate several cellular mechanisms through deacetylation of several transcription factors and enzymes. Recently, Sirt2 was shown to prevent the development of inflammatory processes and its expression favors acute Listeria monocytogenes infection. The impact of this molecule in the context of chronic infections remains unknown. We found that specific Sirt2 deletion in the myeloid lineage transiently increased Mycobacterium tuberculosis load in the lungs and liver of conditional mice. Sirt2 did not affect long-term infection since no significant differences were observed in the bacterial burden at days 60 and 120 post-infection. The initial increase in M. tuberculosis growth was not due to differences in inflammatory cell infiltrates in the lung, myeloid or CD4+ T cells. The transcription levels of IFN-γ, IL-17, TNF, IL-6 and NOS2 were also not affected in the lungs by Sirt2-myeloid specific deletion. Overall, our results demonstrate that Sirt2 expression has a transitory effect in M. tuberculosis infection. Thus, modulation of Sirt2 activity in vivo is not expected to affect chronic infection with M. tuberculosis.
Highlights
Sirtuins (Sirts) are a family of seven NAD+-dependent protein deacetylases in mammalians (Sirt1-Sirt7), distributed by different cellular compartments and enabling cells to deal with several stress conditions [1,2,3]
Previous studies have demonstrated a role of Sirt2 both in inflammation [9,12,14] and in infection by the intracellular pathogen L. monocytogens [15]
Since the control of M. tuberculosis infection is dependent on the activation of macrophages, we questioned whether ablation of Sirt2 in the myeloid lineage would impact the course of M. tuberculosis infection
Summary
Sirtuins (Sirts) are a family of seven NAD+-dependent protein deacetylases in mammalians (Sirt1-Sirt7), distributed by different cellular compartments and enabling cells to deal with several stress conditions [1,2,3]. Sirt and 6 were shown to target several substrates involved in the cellular stress associated to inflammatory responses, such as the transcription factors NF-κB [4,5,6], AP-1 [7] and Foxp3 [8]. Sirt shuttles between cytosol and nucleus effectively removing the acetyl group from lysine 310 of p65 subunit of NF-κB [5] and PLOS ONE | DOI:10.1371/journal.pone.0131904. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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