Loss of selenoprotein W in murine macrophages alters the hierarchy of selenoprotein expression, redox tone, and mitochondrial functions during inflammation

Misra, Santosh; Lee, Tai-Jung; Sebastian, Aswathy; McGuigan, John A. S.; Liao, Chang; Koo, Imhoi; Patterson, Andrew D.; Rossi, Randall M.; Hall, Molly A.; Albert, István; Prabhu, K. Sandeep

doi:10.1016/j.redox.2022.102571

Cited by 14 publications

(4 citation statements)

References 38 publications

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“…This short infection period did demonstrate the anticipated macrophage control of the intracellular bacteria through upregulation of complement genes, Cxcr4 , Aif1 , Maf , and pathway enrichment of oxidative stress, phagosome formation, and HIF1α signaling. However, differential gene expression also revealed upregulation of key genes associated with an anti-inflammatory response, such as Selenop, 71 Lair1, 72 and Gas6, 73 with concurrent upregulation of the NRF2 pathway (Fig5C,D).…”

Section: Resultsmentioning

confidence: 98%

How Mycobacterium tuberculosis builds a home: Single-cell analysis reveals M. tuberculosis ESX-1-mediated accumulation of anti-inflammatory macrophages in infected mouse lungs

Zheng,

Borja,

Dorman

et al. 2024

Preprint

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Mycobacterium tuberculosis (MTB) infects and replicates in lung mononuclear phagocytes (MNPs) with astounding ability to evade elimination. ESX-1, a type VII secretion system, acts as a virulence determinant that contributes to MTB's ability to survive within MNPs, but its effect on MNP recruitment and/or differentiation remains unknown. Here, using single-cell RNA sequencing, we studied the role of ESX-1 in MNP heterogeneity and response in mice and murine bone marrow-derived macrophages (BMDM). We found that ESX-1 is required for MTB to recruit diverse MNP subsets with high MTB burden. Further, MTB induces an anti-inflammatory signature in MNPs and BMDM in an ESX-1 dependent manner. Similarly, spatial transcriptomics revealed an upregulation of anti-inflammatory signals in MTB lesions, where monocyte-derived macrophages concentrate near MTB-infected cells. Together, our findings suggest that MTB ESX-1 mediates the recruitment and differentiation of anti-inflammatory MNPs, which MTB can infect and manipulate for survival.

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Section: Resultsmentioning

confidence: 98%

How Mycobacterium tuberculosis builds a home: Single-cell analysis reveals M. tuberculosis ESX-1-mediated accumulation of anti-inflammatory macrophages in infected mouse lungs

Zheng,

Borja,

Dorman

et al. 2024

Preprint

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“…Meanwhile, our results showed no expression of Arginase 1 (Arg 1) in RAW264.7 infected by S. suis (Figure S4). During the pathogenic bacteria invasion, macrophages should switch to the M1 type which did not express Arg 1 but express iNOS [ 31 , 32 ]. So our results also confirmed the situation of RAW264.7 in the phagocytosis experiment is M1 type.…”

Section: Resultsmentioning

confidence: 99%

Streptococcal arginine deiminase system defences macrophage bactericidal effect mediated by XRE family protein XtrSs

Zhang,

Liang,

Zhang

et al. 2024

Virulence

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The arginine deiminase system (ADS) has been identified in various bacteria and functions to supplement energy production and enhance biological adaptability. The current understanding of the regulatory mechanism of ADS and its effect on bacterial pathogenesis is still limited. Here, we found that the XRE family transcriptional regulator XtrSs negatively affected Streptococcus suis virulence and significantly repressed ADS transcription when the bacteria were incubated in blood. Electrophoretic mobility shift (EMSA) and lacZ fusion assays further showed that XtrSs directly bind to the promoter of ArgR, an acknowledged positive regulator of bacterial ADS, to repress ArgR transcription. Moreover, we provided compelling evidence that S. suis could utilize arginine via ADS to adapt to acid stress, while Δ xtrSs enhanced this acid resistance by upregulating the ADS operon. Moreover, whole ADS-knockout S. suis increased arginine and antimicrobial NO in the infected macrophage cells, decreased intracellular survival, and even caused significant attenuation of bacterial virulence in a mouse infection model, while Δ xtrSs consistently presented the opposite results. Our experiments identified a novel ADS regulatory mechanism in S. suis , whereby XtrSs regulated ADS to modulate NO content in macrophages, promoting S. suis intracellular survival. Meanwhile, our findings provide a new perspective on how Streptococci evade the host’s innate immune system.

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“…Depletion of selenoprotein W leads to impaired osteoclast formation and bone resorption, likely due to the reliance of these macrophages on oxidative phosphorylation for energy production and the consequential impact of selenoprotein W deletion on the glycolytic metabolism during osteoclastogenesis [34].…”

Section: Discussionmentioning

confidence: 99%

Selenium nanoparticles ameliorate lumbar disc degeneration by restoring GPX1-mediated redox homeostasis and mitochondrial function of nucleus pulposus cells

He,

Tian,

Zhou

et al. 2024

Preprint

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Intervertebral disc degeneration (IVDD) is a prevalent musculoskeletal disorder that involves the excessive accumulation of reactive oxygen species (ROS), resulting in mitochondrial dysfunction and matrix metabolism imbalance in nucleus pulposus cells (NPCs). Selenium, an indispensable trace element, plays a crucial role in maintaining mitochondrial redox homeostasis by being incorporated into antioxidant selenoproteins as selenocysteine. In this study, we employed a straightforward synthesis method to produce selenium nanoparticles (SeNPs) with consistent size and distribution, and evaluated their potential protective effects in ameliorating IVDD. In a simulated inflammatory environment induced by interleukin-1beta (IL-1β) in vitro, SeNPs demonstrated a protective effect on the matrix synthesis capacity of NPCs through the up-regulation of aggrecan and type II collagen, while concurrently suppressing the expression of matrix degradation enzymes including MMP13 and ADAMTS5. Additionally, SeNPs preserved mitochondrial integrity and restored impaired mitochondrial energy metabolism by activating glutathione peroxidase1 (GPX1) to rebalance redox homeostasis. In a rat lumbar disc model induced by puncture, the local administration of SeNPs preserved the hydration of nucleus pulposus tissue, promoted matrix deposition, and effectively mitigated the progression of IVDD. Our results indicate that the enhancement of GPX1 by SeNPs may offer a promising therapeutic approach for IVDD by restoring mitochondrial function and redox homeostasis.

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Loss of selenoprotein W in murine macrophages alters the hierarchy of selenoprotein expression, redox tone, and mitochondrial functions during inflammation

Cited by 14 publications

References 38 publications

How Mycobacterium tuberculosis builds a home: Single-cell analysis reveals M. tuberculosis ESX-1-mediated accumulation of anti-inflammatory macrophages in infected mouse lungs

How Mycobacterium tuberculosis builds a home: Single-cell analysis reveals M. tuberculosis ESX-1-mediated accumulation of anti-inflammatory macrophages in infected mouse lungs

Streptococcal arginine deiminase system defences macrophage bactericidal effect mediated by XRE family protein XtrSs

Selenium nanoparticles ameliorate lumbar disc degeneration by restoring GPX1-mediated redox homeostasis and mitochondrial function of nucleus pulposus cells

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