title: Myeloid Sirtuin 2 Expression Does Not Impact Long-Term Mycobacterium tuberculosis Control.
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.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Filipa
authors.initials: F
authors.lastname: Cardoso
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Flávia
authors.initials: F
authors.lastname: Castro
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Lúcia
authors.initials: L
authors.lastname: Moreira-Teixeira
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Sousa
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Egídio
authors.initials: E
authors.lastname: Torrado
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Silvestre
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: António Gil
authors.initials: AG
authors.lastname: Castro
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Margarida
authors.initials: M
authors.lastname: Saraiva
authors.affiliation: Instituto de Medicina Molecular, Av. Prof. Egas Moniz, Lisbon, Portugal.
authors.forename: Teresa F
authors.initials: TF
authors.lastname: Pais
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D017353:Gene Deletion; D005786:Gene Expression Regulation; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D008297:Male; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D022423:Myeloid Cells / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D056565:Sirtuin 2 / Q000378:metabolism*; D014397:Tuberculosis, Pulmonary / Q000378:metabolism* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C098680:Il17a protein, mouse; D020381:Interleukin-17; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C418743:Sirt2 protein, mouse; D056565:Sirtuin 2