Pathogens MenTORing Macrophages and Dendritic Cells: Manipulation of mTOR and Cellular Metabolism to Promote Immune Escape

Nouwen, Lonneke; Everts, Bart

doi:10.3390/cells9010161

Cited by 30 publications

(25 citation statements)

References 190 publications

(242 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the helminth B. malayi, it has been reported the mTORC1 inhibition in DCs through secreted rapamycin-like molecules, which induced a significant downregulation of p70S6K and 4EBP1 phosphorylation and impaired the synthesis of IL-12 and IL-10 reducing their CD4 + T cell-activating capacity 33 . On the other hand, and in concordance with this work, Toxoplasma gondii-infected macrophages induced the mTORC1 activation increasing translation of pro-inflammatory cytokines such as IL-6, and also cytokines as IL-10, with antiinflammatory feature 63 .…”

Section: Discussionsupporting

confidence: 88%

Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition

Rodrígues

Nicolao

Chop

et al. 2020

Preprint

View full text Add to dashboard Cite

1.AbstractImmune evasion is a hallmark of persistent echinococcal infection, comprising modulation of innate immune cells and antigen-specific T cell responses. However, recognition of Echinococcus granulosus by dendritic cells (DCs) is a key determinant of the host’s response to this parasite. Given that mTOR signaling pathway has been described as a regulator linking metabolism and immune function in DCs, we reported for the first time in these cells, global translation levels, antigen uptake, phenotype, cytokine transcriptional levels, and splenocyte priming activity upon recognition of the hydatid fluid (HF) and the highly glycosylated laminar layer (LL). We found that LL induced a slight up-regulation of CD86 and MHC II in DCs and also stimulated the production of IL-6 and TNF-α. By contrast, HF did not increase the expression of any co-stimulatory molecules, but also down-modulated CD40 and stimulated the expression of the anti-inflammatory cytokine IL-10. Both parasitic antigens promoted protein synthesis through mTOR activation. The use of rapamycin decreased the expression of the cytokines tested, empowered the down-modulation of CD40 and also reduced splenocyte proliferation. Finally, we showed that E. granulosus antigens increase the amounts of LC3-positive structures in DCs which play critical roles in the presentation of these antigens to T cells.

show abstract

Section: Discussionsupporting

confidence: 88%

Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition

Rodrígues

Nicolao

Chop

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…In addition, mTOR inhibitor rapamycin also enhances the magnitude and quality of viralspecific CD8+ T-cell responses to vaccination in macaques. 39 severity. The neutrophil-to-lymphocyte ratio (NLR) in patients with COVID-19 is an early warning indicator of the development of severe disease.…”

Section: Therapeutic Potential Of Mechanistic Target Of Rapamycin Imentioning

confidence: 99%

Immunoregulation with mTOR inhibitors to prevent COVID‐19 severity: A novel intervention strategy beyond vaccines and specific antiviral medicines

Zheng¹,

Liu

2020

Journal of Medical Virology

View full text Add to dashboard Cite

Coronavirus disease 2019 (COVID-19) has become a major global public health concern. The mortality rate for critically ill patients is up to 60%, and, thus, reducing the disease severity and case mortality is a top priority. Currently, cytokine storms are considered as the major cause of critical illness and death due to COVID-19.After a systematical review of the literature, we propose that cross-reactive antibodies associated with antibody-dependent enhancement (ADE) may actually be the cause of cytokine storms. It would be more difficult to develop vaccines for highly pathogenic human coronaviruses (CoVs) if ADE characteristics are taken into consideration. Therefore, it is urgent to find an effective way to prevent the occurrence of severe illness as severe acute respiratory syndrome CoV-2 specific drugs or vaccines are still in development. If the activation of memory B cells can be selectively inhibited in high-risk patients at an early stage of COVID-19 to reduce the production of cross-reactive antibodies against the virus, we speculate that ADE can be circumvented and severe symptoms can be prevented. The mammalian target of rapamycin (mTOR) inhibitors satisfy such needs and it is recommended to conduct clinical trials for mTOR inhibitors in preventing the severity of COVID-19. K E Y W O R D S ADE, antibody-dependent enhancement, coronavirus, cross-reactive antibody, cytokine storm, immunity, mTOR inhibitors, rapamycin How to cite this article: Zheng Y, Li R, Liu S. Immunoregulation with mTOR inhibitors to prevent COVID-19 severity: A novel intervention strategy beyond vaccines and specific antiviral medicines.

show abstract

“…However, it is now recognized that rapamycin is best identified as an immunomodulator rather than an immunosuppressant [44,87]. Because of its use in transplant patients and its potential anti-aging role, there has been a large number of studies on the effect of rapamycin and mTOR signaling on various aspects of the immune system, and there have been several recent review articles in this area [88][89][90][91]. In this review, we will focus on those studies that have evaluated the effect of rapamycin treatment on the ability of an animal to respond to an antigen/vaccine or infectious agent.…”

Section: Effect Of Rapamycin On the Immune Response To Infectious Agementioning

confidence: 99%

Effect of rapamycin on aging and age-related diseases—past and future

2020

View full text Add to dashboard Cite

In 2009, rapamycin was reported to increase the lifespan of mice when implemented later in life. This observation resulted in a sea-change in how researchers viewed aging. This was the first evidence that a pharmacological agent could have an impact on aging when administered later in life, i.e., an intervention that did not have to be implemented early in life before the negative impact of aging. Over the past decade, there has been an explosion in the number of reports studying the effect of rapamycin on various diseases, physiological functions, and biochemical processes in mice. In this review, we focus on those areas in which there is strong evidence for rapamycin’s effect on aging and age-related diseases in mice, e.g., lifespan, cardiac disease/function, central nervous system, immune system, and cell senescence. We conclude that it is time that pre-clinical studies be focused on taking rapamycin to the clinic, e.g., as a potential treatment for Alzheimer’s disease.

show abstract

Pathogens MenTORing Macrophages and Dendritic Cells: Manipulation of mTOR and Cellular Metabolism to Promote Immune Escape

Cited by 30 publications

References 190 publications

Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition

Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition

Immunoregulation with mTOR inhibitors to prevent COVID‐19 severity: A novel intervention strategy beyond vaccines and specific antiviral medicines

Effect of rapamycin on aging and age-related diseases—past and future

Contact Info

Product

Resources

About