High rates of serum selenium deficiency among HIV- and HCV-infected and uninfected drug users in Buenos Aires, Argentina – Corrigendum

Sheehan, Heidi; Benetucci, Jorge; Muzzio, Estela; Redini, Liliana; Naveira, Jorge; Segura, Marcela; Weissenbacher, Mercedes; Tang, Alice

doi:10.1017/s1368980011002357

Cited by 2 publications

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“…While selenoproteins promote normal growth, immunity, and reproductive health in humans (11), the ability of Sesupplementation and therefore, selenoproteins of the host to limit infectious disease severity has also been demonstrated in nutritional intervention studies (12)(13)(14)(15)(16)(17)(18)(19)(20). Se deficiency is associated with chronic infections caused by HIV/AIDS, hepatitis C virus, and Mycobacterium tuberculosis (12)(13)(14)(15); nutritional interventions that contain Se have benefitted patients (16)(17)(18)(19)(20). However, many of these studies did not test the change in expression of selenoproteins following intervention.…”

Section: Introductionmentioning

confidence: 99%

Macrophage Selenoproteins Restrict Intracellular Replication of Francisella tularensis and Are Essential for Host Immunity

et al. 2021

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The essential micronutrient Selenium (Se) is co-translationally incorporated as selenocysteine into proteins. Selenoproteins contain one or more selenocysteines and are vital for optimum immunity. Interestingly, many pathogenic bacteria utilize Se for various biological processes suggesting that Se may play a role in bacterial pathogenesis. A previous study had speculated that Francisella tularensis, a facultative intracellular bacterium and the causative agent of tularemia, sequesters Se by upregulating Se-metabolism genes in type II alveolar epithelial cells. Therefore, we investigated the contribution of host vs. pathogen-associated selenoproteins in bacterial disease using F. tularensis as a model organism. We found that F. tularensis was devoid of any Se utilization traits, neither incorporated elemental Se, nor exhibited Se-dependent growth. However, 100% of Se-deficient mice (0.01 ppm Se), which express low levels of selenoproteins, succumbed to F. tularensis-live vaccine strain pulmonary challenge, whereas 50% of mice on Se-supplemented (0.4 ppm Se) and 25% of mice on Se-adequate (0.1 ppm Se) diet succumbed to infection. Median survival time for Se-deficient mice was 8 days post-infection while Se-supplemented and -adequate mice was 11.5 and >14 days post-infection, respectively. Se-deficient macrophages permitted significantly higher intracellular bacterial replication than Se-supplemented macrophages ex vivo, corroborating in vivo observations. Since Francisella replicates in alveolar macrophages during the acute phase of pneumonic infection, we hypothesized that macrophage-specific host selenoproteins may restrict replication and systemic spread of bacteria. F. tularensis infection led to an increased expression of several macrophage selenoproteins, suggesting their key role in limiting bacterial replication. Upon challenge with F. tularensis, mice lacking selenoproteins in macrophages (TrspM) displayed lower survival and increased bacterial burden in the lung and systemic tissues in comparison to WT littermate controls. Furthermore, macrophages from TrspM mice were unable to restrict bacterial replication ex vivo in comparison to macrophages from littermate controls. We herein describe a novel function of host macrophage-specific selenoproteins in restriction of intracellular bacterial replication. These data suggest that host selenoproteins may be considered as novel targets for modulating immune response to control a bacterial infection.

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