scholarly journals Indoleamine 2,3-Dioxygenase Is Involved in Interferon Gamma’s Anti-BKPyV Activity in Renal Cells

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 865
Author(s):  
Tony Fiore ◽  
Elodie Martin ◽  
Véronique Descamps ◽  
Etienne Brochot ◽  
Virginie Morel ◽  
...  

Reactivation of BK polyomavirus (BKPyV) infection is frequently increasing in transplant recipients treated with potent immunosuppressants and highlights the importance of immune system components in controlling viral reactivation. However, the immune response to BKPyV in general and the role of antiviral cytokines in infection control in particular are poorly understood. Here, we investigated the efficacy of interferons (IFN) alpha, lambda and gamma with regard to the BKPyV multiplication in Vero cells. Treatment with IFN-gamma inhibited the expression of the viral protein VP1 in a dose-dependent manner and decreased the expression of early and late viral transcripts. Viral inhibition by IFN-gamma was confirmed in human cells (Caki-1 cells and renal proximal tubular epithelial cells). One of the IFN-stimulated genes most strongly induced by IFN-gamma was the coding for the enzyme indoleamine 2,3 dioxygenase (IDO), which is known to limit viral replication and regulates the host immune system. The antiviral activity induced by IFN-gamma could be reversed by the addition of an IDO inhibitor, indicating that IDO has a specific role in anti-BKPyV activity. A better understanding of the action mechanism of these IFN-gamma-induced antiviral proteins might facilitate the development of novel therapeutic strategies.

2020 ◽  
Vol 19 (7) ◽  
pp. 509-526
Author(s):  
Qin Huang ◽  
Fang Yu ◽  
Di Liao ◽  
Jian Xia

: Recent studies implicate microbiota-brain communication as an essential factor for physiology and pathophysiology in brain function and neurodevelopment. One of the pivotal mechanisms about gut to brain communication is through the regulation and interaction of gut microbiota on the host immune system. In this review, we will discuss the role of microbiota-immune systeminteractions in human neurological disorders. The characteristic features in the development of neurological diseases include gut dysbiosis, the disturbed intestinal/Blood-Brain Barrier (BBB) permeability, the activated inflammatory response, and the changed microbial metabolites. Neurological disorders contribute to gut dysbiosis and some relevant metabolites in a top-down way. In turn, the activated immune system induced by the change of gut microbiota may deteriorate the development of neurological diseases through the disturbed gut/BBB barrier in a down-top way. Understanding the characterization and identification of microbiome-immune- brain signaling pathways will help us to yield novel therapeutic strategies by targeting the gut microbiome in neurological disease.


2021 ◽  
Vol 17 (8) ◽  
pp. e1009839
Author(s):  
Andrew S. Wagner ◽  
Trevor J. Hancock ◽  
Stephen W. Lumsdaine ◽  
Sarah J. Kauffman ◽  
Mikayla M. Mangrum ◽  
...  

Masking the immunogenic cell wall epitope ß(1,3)-glucan under an outer layer of mannosylated glycoproteins is an important virulence factor deployed by Candida albicans during infection. Consequently, increased ß(1,3)-glucan exposure (unmasking) reveals C. albicans to the host’s immune system and attenuates its virulence. We have previously shown that activation of the Cek1 MAPK pathway via expression of a hyperactive allele of an upstream kinase (STE11ΔN467) induces unmasking. It also increased survival of mice in a murine disseminated candidiasis model and attenuated kidney fungal burden by ≥33 fold. In this communication, we utilized cyclophosphamide-induced immunosuppression to test if the clearance of the unmasked STE11ΔN467 mutant was dependent on the host immune system. Suppression of the immune response by cyclophosphamide reduced the attenuation in fungal burden caused by the STE11ΔN467 allele. Moreover, specific depletion of neutrophils via 1A8 antibody treatment also reduced STE11ΔN467-dependent fungal burden attenuation, but to a lesser extent than cyclophosphamide, demonstrating an important role for neutrophils in mediating fungal clearance of unmasked STE11ΔN467 cells. In an effort to understand the mechanism by which Ste11ΔN467 causes unmasking, transcriptomics were used to reveal that several components in the Cek1 MAPK pathway were upregulated, including the transcription factor CPH1 and the cell wall sensor DFI1. In this report we show that a cph1ΔΔ mutation restored ß(1,3)-glucan exposure to wild-type levels in the STE11ΔN467 strain, confirming that Cph1 is the transcription factor mediating Ste11ΔN467-induced unmasking. Furthermore, Cph1 is shown to induce a positive feedback loop that increases Cek1 activation. In addition, full unmasking by STE11ΔN467 is dependent on the upstream cell wall sensor DFI1. However, while deletion of DFI1 significantly reduced Ste11ΔN467-induced unmasking, it did not impact activation of the downstream kinase Cek1. Thus, it appears that once stimulated by Ste11ΔN467, Dfi1 activates a parallel signaling pathway that is involved in Ste11ΔN467-induced unmasking.


Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1380
Author(s):  
Daniel Sausen ◽  
Maimoona Bhutta ◽  
Elisa Gallo ◽  
Harel Dahari ◽  
Ronen Borenstein

Epstein-Barr virus (EBV) is typically found in a latent, asymptomatic state in immunocompetent individuals. Perturbations of the host immune system can stimulate viral reactivation. Furthermore, there are a myriad of EBV-associated illnesses including various cancers, post-transplant lymphoproliferative disease, and autoimmune conditions. A thorough understanding of this virus, and the interplay between stress and the immune system, is essential to establish effective treatment. This review will provide a summary of the interaction between both psychological and cellular stressors resulting in EBV reactivation. It will examine mechanisms by which EBV establishes and maintains latency and will conclude with a brief overview of treatments targeting EBV.


2020 ◽  
Vol 11 (SPL1) ◽  
pp. 259-261
Author(s):  
Aamir Khan ◽  
Rajni K. Gurmule

Vasavaleha is one of the best medicine given for respiratory diseases. Corona viruses typically affect the respiratory system, causing symptoms such as coughing, fever and shortness of breath. It also affects host immune system of human body. Spreading rate of this disease is very high. Whole world is seeking for the treatment which can uproots this diseases. There in no vaccine available till date against this pandemic disease. Ayurveda mainly focuses on prevention of diseases alongwith its total cure. Rajyakshma Vyadhi is MadhyamMarga Roga as per Ayurveda. It shows many symptoms such as Kasa, Shwasa etc. By overall view of Covid 19, shows its resemblance with Rajyakshma Vyadhi described in Ayurveda. Vasavaleha is a Kalpa which is described in Rogadhikara of Rajyakshma. It shows Kasahara, Shwashara properties. It consists of Vasa, Pipalli, Madhu and Goghrita. These components shows actions like bronchodilation, antitussive effect and many more other actions. Pipalli shows important Rasayana effect. So in present review, we have tried to focus on role of Vasavaleha in the management of Covid 19. This can be used as preventive as well as adjuvant medication in treating Covid 19. There is need of further clinical research to rule of exact action of Vasavaleha against Covid 19.


Author(s):  
Malireddy S Reddy

The worldwide popularity of Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy to treat or prevent the hospital acquired infections (nosocomial infections) arose a great interest in the medical community around the world (Reddy and Reddy, 2016; 2017). The following questions were raised on this subject: Does Multiple Mixed Strain Probiotics directly inhibit the pathogenic bacteria (C. diff) in the gastrointestinal tract or indirectly through modulation of the host immune system or both? To be more specific, what is the exact and/or hypothetical mechanism at molecular level behind the breakthrough discovery of Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy?  To answer these questions, the specific immunomodulation regulatory functions of the individual Probiotic strains (on host) have beenresearched, investigated andoutlined in this article.  A detailed explanation(s) and hypotheses have been proposed outlining the possible cumulativedirect bacteriological and indirect immunomodulatory effects (at the molecular level) of the Multiple Mixed Strain Probiotics used in Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy to successfully treat C. diff infection.  A detailed scientific and research attempts were made to correlate the Probiotic induced immune activities in relation to the reduction of the symptoms associated with the hospital acquired Clostridium difficile infection during and after the Multiple Mixed Strain Probioitc Therapy.  Results of the clinical trials, microbiological tests on feces, and the clinical blood tests significantly revealed that the reasons for the success of Dr. Reddy’s Multiple Mixed Strain Probiotic Therapy are multifold. Presumably, it is predominantly due to the immunomodulatory effect they have exerted on the host immune system along with the direct inhibition of C. diff bacteria by multiple Probiotics, due to the production of bacteriocins, lactic acid and nutritional competency.In addition, the size of the individual cells of the Probiotic strains in the Multiple Mixed Strain Probiotics and their significant effect on immunomodulation has been thoroughly discussed. Results clearly proved that if Probiotics are absent in the GI tract during C. diff infection, the chances of patient survival is zero.  This is because of the excess immune stimulation and incurable damage to the epithelial cell barrier of the gastrointestinal tract caused by C. diff bacteria.  The results also revealed, without any doubt, as of to-datethe latest discovery of Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy is the best way to cure the deadly hospital acquired infections affecting millions of people around the world, with high degree of mortality.  This has been attested by several practicng medical professionals and scientists around the world (Reddy and Reddy, 2017).


2020 ◽  
Vol 21 (3) ◽  
pp. 245-264 ◽  
Author(s):  
Laura C. García-Carnero ◽  
José A. Martínez-Álvarez ◽  
Luis M. Salazar-García ◽  
Nancy E. Lozoya-Pérez ◽  
Sandra E. González-Hernández ◽  
...  

: By being the first point of contact of the fungus with the host, the cell wall plays an important role in the pathogenesis, having many molecules that participate as antigens that are recognized by immune cells, and also that help the fungus to establish infection. The main molecules reported to trigger an immune response are chitin, glucans, oligosaccharides, proteins, melanin, phospholipids, and others, being present in the principal pathogenic fungi with clinical importance worldwide, such as Histoplasma capsulatum, Paracoccidioides brasiliensis, Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans, Blastomyces dermatitidis, and Sporothrix schenckii. Knowledge and understanding of how the immune system recognizes and responds to fungal antigens are relevant for the future research and development of new diagnostic tools and treatments for the control of mycosis caused by these fungi.


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