scholarly journals Type I Interferon Transcriptional Signature in Neutrophils and Low-Density Granulocytes Are Associated with Tissue Damage in Malaria

Cell Reports ◽  
2015 ◽  
Vol 13 (12) ◽  
pp. 2829-2841 ◽  
Author(s):  
Bruno Coelho Rocha ◽  
Pedro Elias Marques ◽  
Fabiana Maria de Souza Leoratti ◽  
Caroline Junqueira ◽  
Dhelio Batista Pereira ◽  
...  
Keyword(s):  
Tissue Damage ◽  
Type I Interferon ◽  
Type I ◽  
Low Density ◽  
Transcriptional Signature

scholarly journals A Type I Interferon Transcriptional Signature Precedes Autoimmunity in Children Genetically at Risk for Type 1 Diabetes

Diabetes ◽  
2014 ◽  
Vol 63 (7) ◽  
pp. 2538-2550 ◽  
Author(s):  
R. C. Ferreira ◽  
H. Guo ◽  
R. M. R. Coulson ◽  
D. J. Smyth ◽  
M. L. Pekalski ◽  
...  
Keyword(s):  
At Risk ◽  
Type 1 Diabetes ◽  
Type I Interferon ◽  
Type I ◽  
Transcriptional Signature

ALL-associated JAK1 mutations confer hypersensitivity to the antiproliferative effect of type I interferon

Blood ◽  
2010 ◽  
Vol 115 (16) ◽  
pp. 3287-3295 ◽  
Author(s):  
Tekla Hornakova ◽  
Sabina Chiaretti ◽  
Muriel M. Lemaire ◽  
Robin Foà ◽  
Raouf Ben Abdelali ◽  
...  
Keyword(s):  
Cell Lines ◽  
Type I Interferon ◽  
Type I ◽  
Type I Ifn ◽  
Transcriptional Signature ◽  
Activating Mutations ◽  
Type I Ifns ◽  
Antitumorigenic Effect

Abstract Activating mutations in JAK1 have been reported in acute lymphoblastic leukemias (ALLs). In this study, we found a type I interferon (IFN) transcriptional signature in JAK1 mutation-positive human ALL samples. This signature was recapitulated in vitro by the expression of JAK1 mutants in BW5147 and BaF3 hematopoietic cell lines. Binding of JAK1 to the IFN receptor was essential because mutations in the FERM domain abrogated this effect. Beside the constitutive activation of the type I IFN signaling cascade, JAK1 mutations also strongly potentiated the response to IFN in vitro. Typically, the proliferation of cell lines expressing JAK1A634D was abrogated by type I IFNs. Interestingly, we found that different JAK1 mutations differentially potentiate responses to type I IFNs or to interleukin-9, another cytokine using JAK1 to mediate its effects. This suggests that the type of mutation influences the specificity of the effect on distinct cytokine receptor signaling. Finally, we also showed in an in vivo leukemia model that cells expressing JAK1A634D are hypersensitive to the antiproliferative and antitumorigenic effect of type I IFN, suggesting that type I IFNs should be considered as a potential therapy for ALL with JAK1-activating mutations.

scholarly journals SOCS-1 inhibition of type I interferon limits Staphylococcus aureus skin host defense

2020 ◽  
Author(s):  
Nathan Klopfenstein ◽  
Stephanie Brandt ◽  
Sydney Castellanos ◽  
C. Henrique Serezani
Keyword(s):  
Staphylococcus Aureus ◽  
Host Defense ◽  
Tissue Damage ◽  
Skin Infection ◽  
Type I Interferon ◽  
Microbial Control ◽  
Cytokine Signaling ◽  
Type I ◽  
Bacterial Killing

AbstractThe innate immune response to methicillin-resistant Staphylococcus aureus (MRSA) skin infection culminates in forming an abscess that prevents the bacterial spread and tissue damage. Pathogen recognition receptors (PRRs) dictate the balance between microbial control and tissue damage. Therefore, intracellular brakes are of fundamental importance to tune the appropriate host defense while preventing injury. The intracellular inhibitor suppressor of cytokine signaling 1 (SOCS-1); is a classic JAK/STAT inhibitor that prevents PRR responses by influencing the expression and actions of PRR adaptors and downstream effectors. Whether SOCS-1 is a molecular component of skin host defense remains to be determined. Here, we hypothesized that SOCS-1 decreases type I interferon production and IFNAR-mediated antimicrobial effector functions of the inflammatory response during MRSA skin infection. Our data show that MRSA skin infection enhances SOCS-1 expression, and both SOCS-1 inhibitor peptide treated and myeloid-specific SOCS-1 deficient mice display decreased lesion size, bacterial loads, and increased abscess thickness when compared to wild-type mice treated or not with scrambled peptide control. SOCS-1 deletion/inhibition increases phagocytosis and bacterial killing, dependent on nitric oxide release. SOCS-1 inhibition also increases antimicrobial effector function correlated with type I and type II interferon levels in vivo. IFNAR deletion and antibody blockage abolished the beneficial effects of SOCS-1 inhibition in vivo. Notably, we unveiled that hyperglycemia triggers aberrant SOCS-1 expression that correlates with decreased overall IFN signatures in the skin. SOCS-1 inhibition restores skin host defense in highly susceptible hyperglycemic mice. Overall, these data demonstrate a role for type I interferons in enhancing microbial clearance and host defense during MRSA skin infection.

scholarly journals cGAS-STING Signaling Pathway Mediates Brain Trauma-Induced Type I Interferon Response

2021 ◽  
Author(s):  
Lauren Fritsch ◽  
Jing Ju ◽  
Erwin Kristobal Gudenschwager Basso ◽  
Eman Soliman ◽  
Swagatika Paul ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Tissue Damage ◽  
Type I Interferon ◽  
Interferon Response ◽  
Motor Deficit ◽  
Type I ◽  
Post Injury ◽  
Interferon Stimulated Genes ◽  
Molecular Pattern ◽  
Signaling Axis

Abstract Background Inflammation is a key contributor of neuronal death and dysfunction following traumatic brain injury (TBI). Recent evidence suggests that interferons may be a key regulator of this response. Our studies evaluated the role of the Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes (cGAS-STING) signaling pathway a murine model of TBI. Methods Male, eight-week old wildtype, STING knockout ( -/- ), cGAS -/- , and NLRX1 -/- mice were subjected to controlled cortical impact (CCI) or sham injury. Histopathological evaluation of tissue damage was assessed using non-biased stereology, which was complemented by analysis at the mRNA and protein level using qPCR and western blot analysis, respectively. Results We found that STING and Type I interferon-stimulated genes were upregulated after CCI injury in a bi-phasic manner and that loss of cGAS or STING conferred neuroprotection concomitant with a blunted inflammatory response at 24 hours post-injury. cGAS -/- animals showed reduced motor deficit 4 days after injury (dpi), and amelioration of tissue damage was seen in both groups of mice up to 14 dpi. Given that cGAS requires a cytosolic damage- or pathogen- associated molecular pattern (DAMP/PAMP) to prompt downstream STING signaling, we further show that mitochondrial DNA is present in the cytosol after TBI. Finally, our findings demonstrate that NLRX1 may be an additional regulator that functions upstream to regulate cGASSTING pathway. Conclusions These findings suggest that the canonical cGAS-STING-mediated Type I interferon signaling axis is a critical component of neural tissue damage following TBI and that mtDNA may be a possible trigger in this response.

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