Sirtuin 1 Regulates Dendritic Cell Activation and Autophagy during Respiratory Syncytial Virus–Induced Immune Responses

Owczarczyk, Anna B.; Schaller, Matthew; Reed, Michelle; Rasky, Andrew J.; Lombard, David B.; Lukacs, Nicholas W.

doi:10.4049/jimmunol.1500326

Cited by 59 publications

(62 citation statements)

References 55 publications

(66 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Since RSV induces autophagy (Morris et al, 2011; Reed et al, 2013; Owczarczyk et al, 2015), we next examined a possible role of autophagy in positively regulating TGF-β production during RSV infection.…”

Section: Resultsmentioning

confidence: 99%

“…These results suggested a role of autophagy in IFN-β production from infected macrophages. Interestingly, autophagy induction was required for optimal IFN-β production from RSV infected dendritic cells (DCs) and mouse airway (Morris et al, 2011; Reed et al, 2013; Owczarczyk et al, 2015). However, autophagy induction has not been studied yet in RSV infected macrophages.…”

Section: Resultsmentioning

confidence: 99%

“…RSV induces autophagy in dendritic cells (DCs) and in the respiratory tract of infected mice (Morris et al, 2011; Reed et al, 2013; Owczarczyk et al, 2015). Autophagy is required for efficient IFN-β response during RSV infection, since lack of autophagy reduces IFN-β release from RSV infected DCs.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Autophagy, TGF-β, and SMAD-2/3 Signaling Regulates Interferon-β Response in Respiratory Syncytial Virus Infected Macrophages

Pokharel

Shil

Bose

2016

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Human respiratory syncytial virus (RSV) is a lung tropic virus causing severe airway diseases including bronchiolitis and pneumonia among infants, children, and immuno-compromised individuals. RSV triggers transforming growth factor-β (TGF-β) production from lung epithelial cells and TGF-β facilitates RSV infection of these cells. However, it is still unknown whether RSV infected myeloid cells like macrophages produce TGF-β and the role of TGF-β if any during RSV infection of these cells. Our study revealed that RSV infected macrophages produce TGF-β and as a consequence these cells activate TGF-β dependent SMAD-2/3 signaling pathway. Further mechanistic studies illustrated a role of autophagy in triggering TGF-β production from RSV infected macrophages. In an effort to elucidate the role of TGF-β and SMAD-2/3 signaling during RSV infection, we surprisingly unfolded the requirement of TGF-β—SMAD2/3 signaling in conferring optimal innate immune antiviral response during RSV infection of macrophages. Type-I interferon (e.g., interferon-β or IFN-β) is a critical host factor regulating innate immune antiviral response during RSV infection. Our study revealed that loss of TGF-β—SMAD2/3 signaling pathway in RSV infected macrophages led to diminished expression and production of IFN-β. Inhibiting autophagy in RSV infected macrophages also resulted in reduced production of IFN-β. Thus, our studies have unfolded the requirement of autophagy—TGF-β—SMAD2/3 signaling network for optimal innate immune antiviral response during RSV infection of macrophages.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Autophagy, TGF-β, and SMAD-2/3 Signaling Regulates Interferon-β Response in Respiratory Syncytial Virus Infected Macrophages

Pokharel

Shil

Bose

2016

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…A recent study provided several pieces of evidence indicating a role for SIRT1 in restricting RSV infection in a mouse model . First, RSV infection increased SIRT1 transcription in dendritic cells of infected mice.…”

Section: Sirtuins and Virusesmentioning

confidence: 99%

Resveratrol, sirtuins, and viruses

Yang

Zhang

et al. 2015

Reviews in Medical Virology

View full text Add to dashboard Cite

Resveratrol is a natural phenolic product found in some plants in response to stress and has been linked to the many health benefits of red wine. Over the past several decades, a great deal of research has identified diverse biological roles associated with resveratrol, including anti-oxidant, anti-proliferation, anti-inflammation, anti-cancer, anti-fungal, and antiviral activities. Such biological activities of resveratrol are likely mediated through multiple cellular targets or pathways, such as sirtuins, a family of NAD(+)-dependent deacetylases. In this treatise, the literatures focusing on the roles of resveratrol and sirtuins in modulating infections by a broad-spectrum of viruses are reviewed, with an emphasis on its potential antiviral mechanisms. A working model about the effects of resveratrol on virus infection is proposed to stimulate further researches on this exciting topic.

show abstract

“…Conversely, the enzymatic activity of Sirt1 can be enhanced by small molecule activators including the natural polyphenol, resveratrol, and synthetic Sirt1 activator compounds (151). In respiratory syncytial virus infection, Sirt1 promotes an effective antiviral response through DC cytokine secretion and autophagy-mediated processes, providing an option for a novel vaccination strategy, such as a Sirt1-activating viral vaccine (152). …”

Section: Targeting Cell Regulatory Pathways and Immune Checkpoints Asmentioning

confidence: 99%

Adjunct Strategies for Tuberculosis Vaccines: Modulating Key Immune Cell Regulatory Mechanisms to Potentiate Vaccination

Jayashankar

Hafner

2016

Front. Immunol.

View full text Add to dashboard Cite

Tuberculosis (TB) remains a global health threat of alarming proportions, resulting in 1.5 million deaths worldwide. The only available licensed vaccine, Bacillus Calmette–Guérin, does not confer lifelong protection against active TB. To date, development of an effective vaccine against TB has proven to be elusive, and devising newer approaches for improved vaccination outcomes is an essential goal. Insights gained over the last several years have revealed multiple mechanisms of immune manipulation by Mycobacterium tuberculosis (Mtb) in infected macrophages and dendritic cells that support disease progression and block development of protective immunity. This review provides an assessment of the known immunoregulatory mechanisms altered by Mtb, and how new interventions may reverse these effects. Examples include blocking of inhibitory immune cell coreceptor checkpoints (e.g., programed death-1). Conversely, immune mechanisms that strengthen immune cell effector functions may be enhanced by interventions, including stimulatory immune cell coreceptors (e.g., OX40). Modification of the activity of key cell “immunometabolism” signaling pathway molecules, including mechanistic target of rapamycin, glycogen synthase kinase-3β, wnt/β-catenin, adenosine monophosophate-activated protein kinase, and sirtuins, related epigenetic changes, and preventing induction of immune regulatory cells (e.g., regulatory T cells, myeloid-derived suppressor cells) are powerful new approaches to improve vaccine responses. Interventions to favorably modulate these components have been studied primarily in oncology to induce efficient antitumor immune responses, often by potentiation of cancer vaccines. These agents include antibodies and a rapidly increasing number of small molecule drug classes that have contributed to the dramatic immune-based advances in treatment of cancer and other diseases. Because immune responses to malignancies and to Mtb share many similar mechanisms, studies to improve TB vaccine responses using interventions based on “immuno-oncology” are needed to guide possible repurposing. Understanding the regulation of immune cell functions appropriated by Mtb to promote the imbalance between protective and pathogenic immune responses may guide the development of innovative drug-based adjunct approaches to substantially enhance the clinical efficacy of TB vaccines.

show abstract

Sirtuin 1 Regulates Dendritic Cell Activation and Autophagy during Respiratory Syncytial Virus–Induced Immune Responses

Cited by 59 publications

References 55 publications

Autophagy, TGF-β, and SMAD-2/3 Signaling Regulates Interferon-β Response in Respiratory Syncytial Virus Infected Macrophages

Autophagy, TGF-β, and SMAD-2/3 Signaling Regulates Interferon-β Response in Respiratory Syncytial Virus Infected Macrophages

Resveratrol, sirtuins, and viruses

Adjunct Strategies for Tuberculosis Vaccines: Modulating Key Immune Cell Regulatory Mechanisms to Potentiate Vaccination

Contact Info

Product

Resources

About