Candida vaginitis: the importance of mitochondria and type I interferon signalling

ABSTRACTSeverity of sterile inflammation, as seen in acute pancreatitis, is determined by damage-sensing receptors, signalling cascades and cytokine production. Stat2 is a type I interferon signalling mediator that also has interferon-independent roles in murine lipopolysaccharide-induced NF-κB-mediated sepsis. However its role in sterile inflammation is unknown. We hypothesised that Stat2 determines severity of non-infective inflammation in the pancreas.Wild type (WT) and Stat2−/− mice were injected intraperitoneally with cerulein or L-arginine. Specific cytokine-blocking antibodies were used in some experiments. Pancreata and blood were harvested 1h and 24h after the final dose of cerulein and up to 96h post L-arginine. Whole-tissue phosphoproteomic changes were assessed using label-free mass spectrometry. Tissue-specific Stat2 effects were studied in WT/Stat2−/− bone-marrow chimera and using Cre-lox recombination to delete Stat2 in pancreatic and duodenal homeobox 1(Pdx1)-expressing cells.Stat2−/− mice were protected from cerulein- and L-arginine-induced pancreatitis. Protection was independent of type I interferon signalling. Stat2−/− mice had lower cytokine levels including TNFα and IL-10 and reduced NF-kB nuclear localisation in pancreatic tissue compared to WT. Inhibition of TNFα improved (inhibition of IL-10 worsened) cerulein-induced pancreatitis in WT but not Stat2−/− mice. Phosphoproteomics showed down-regulation of mitogen-activated protein kinase (MAPK) mediators but accumulation of Ser412-phosphorylated Tak1. Stat2 deletion in Pdx1-expressing acinar cells (Stat2flox/Pdx1-cre) reduced pancreatic TNFα expression, but not histological injury or serum amylase. WT/Stat2−/− bone-marrow chimera were protected from pancreatitis irrespective of host or recipient genotype.Stat2 loss results in disrupted signalling in pancreatitis, upstream of NF-κB in non-acinar and/or bone marrow derived cells.

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AXL promotes Zika virus infection in astrocytes by antagonizing type I interferon signalling

Nature Microbiology ◽

10.1038/s41564-017-0092-4 ◽

2018 ◽

Vol 3 (3) ◽

pp. 302-309 ◽

Cited By ~ 67

Author(s):

Jian Chen ◽

Yi-feng Yang ◽

Yu Yang ◽

Peng Zou ◽

Jun Chen ◽

...

Keyword(s):

Virus Infection ◽

Zika Virus ◽

Type I Interferon ◽

Type I ◽

Zika Virus Infection ◽

Interferon Signalling

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Sustained Inflammatory Signalling through Stat1/Stat2/IRF9 Is Associated with Amoeboid Phenotype of Melanoma Cells

Cancers ◽

10.3390/cancers12092450 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2450

Author(s):

Aneta Gandalovičová ◽

Anna-Marie Šůchová ◽

Vladimír Čermák ◽

Ladislav Merta ◽

Daniel Rösel ◽

...

Keyword(s):

Cancer Cells ◽

Type I Interferon ◽

Tumour Progression ◽

Tumour Microenvironment ◽

Melanoma Cells ◽

Interferon Response ◽

Type I ◽

Expression Of Genes ◽

Interferon Signalling ◽

Inflammatory Signalling

The invasive behaviour of cancer cells underlies metastatic dissemination; however, due to the large plasticity of invasion modes, it is challenging to target. It is now widely accepted that various secreted cytokines modulate the tumour microenvironment and pro-inflammatory signalling can promote tumour progression. Here, we report that cells after mesenchymal–amoeboid transition show the increased expression of genes associated with the type I interferon response. Moreover, the sustained activation of type I interferon signalling in response to IFNβ mediated by the Stat1/Stat2/IRF9 complex enhances the round amoeboid phenotype in melanoma cells, whereas its downregulation by various approaches promotes the mesenchymal invasive phenotype. Overall, we demonstrate that interferon signalling is associated with the amoeboid phenotype of cancer cells and suggest a novel role of IFNβ in promoting cancer invasion plasticity, aside from its known role as a tumour suppressor.

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Helicase Domain of West Nile Virus NS3 Protein Plays a Role in Inhibition of Type I Interferon Signalling

Viruses ◽

10.3390/v9110326 ◽

2017 ◽

Vol 9 (11) ◽

pp. 326 ◽

Cited By ~ 7

Author(s):

Yin Setoh ◽

Parthiban Periasamy ◽

Nias Peng ◽

Alberto Amarilla ◽

Andrii Slonchak ◽

...

Keyword(s):

West Nile Virus ◽

Type I Interferon ◽

Helicase Domain ◽

Type I ◽

West Nile ◽

Ns3 Protein ◽

Interferon Signalling

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Type I interferon signalling is not required for the induction of endotoxin tolerance

Cytokine ◽

10.1016/j.cyto.2017.01.017 ◽

2017 ◽

Vol 95 ◽

pp. 7-11 ◽

Cited By ~ 4

Author(s):

Yalda Karimi ◽

Sophie M. Poznanski ◽

Fatemeh Vahedi ◽

Branson Chen ◽

Marianne V. Chew ◽

...

Keyword(s):

Type I Interferon ◽

Endotoxin Tolerance ◽

Type I ◽

Interferon Signalling

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The X proteins of bornaviruses interfere with type I interferon signalling

Journal of General Virology ◽

10.1099/vir.0.047175-0 ◽

2013 ◽

Vol 94 (2) ◽

pp. 263-269 ◽

Cited By ~ 9

Author(s):

Jonas Johansson Wensman ◽

Muhammad Munir ◽

Srinivas Thaduri ◽

Katarina Hörnaeus ◽

Muhammad Rizwan ◽

...

Keyword(s):

Type I Interferon ◽

Rna Virus ◽

Luciferase Reporter ◽

Type I ◽

Type I Ifn ◽

X Protein ◽

Wide Range ◽

Reporter Assays ◽

Interferon Signalling

Borna disease virus (BDV) is a neurotropic, negative-stranded RNA virus causing persistent infection and progressive neurological disorders in a wide range of warm-blooded animals. The role of the small non-structural X protein in viral pathogenesis is not completely understood. Here we investigated whether the X protein of BDV and avian bornavirus (ABV) interferes with the type I interferon (IFN) system, similar to other non-structural proteins of negative-stranded RNA viruses. In luciferase reporter assays, we found that the X protein of various bornaviruses interfered with the type I IFN system at all checkpoints investigated, in contrast to previously reported findings, resulting in reduced type I IFN secretion.

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