scholarly journals Anti-Cancer Drug HMBA Acts as an Adjuvant during Intracellular Bacterial Infections by Inducing Type I IFN through STING

2017 ◽  
Vol 199 (7) ◽  
pp. 2491-2502 ◽  
Author(s):  
Akshamal Mihiranga Gamage ◽  
Kok-Onn Lee ◽  
Yunn-Hwen Gan
Keyword(s):  
Bacterial Infections ◽  
Cancer Drug ◽  
Type I ◽  
Type I Ifn ◽  
Anti Cancer

scholarly journals An Anti-Cancer Drug Candidate CYC116 Suppresses Type I Hypersensitive Immune Responses through the Inhibition of Fyn Kinase in Mast Cells

2019 ◽  
Vol 27 (3) ◽  
pp. 311-317 ◽  
Author(s):  
Young Hwan Park ◽  
Hyun Woo Kim ◽  
Hyuk Soon Kim ◽  
Seung Taek Nam ◽  
Dajeong Lee ◽  
...  
Keyword(s):  
Mast Cells ◽  
Immune Responses ◽  
Cancer Drug ◽  
Drug Candidate ◽  
Type I ◽  
Fyn Kinase ◽  
Anti Cancer

scholarly journals Role of the transcriptional regulator SP140 in resistance to bacterial infections via repression of type I interferons

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Daisy X Ji ◽  
Kristen C Witt ◽  
Dmitri I Kotov ◽  
Shally R Margolis ◽  
Alexander Louie ◽  
...  
Keyword(s):  
Legionella Pneumophila ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Negative Regulator ◽  
Type I Interferons ◽  
Type I ◽  
Type I Ifn ◽  
Viral Immunity ◽  
Type I Ifns ◽  
Important Negative Regulator

Type I interferons (IFNs) are essential for anti-viral immunity, but often impair protective immune responses during bacterial infections. An important question is how type I IFNs are strongly induced during viral infections, and yet are appropriately restrained during bacterial infections. The Super susceptibility to tuberculosis 1 (Sst1) locus in mice confers resistance to diverse bacterial infections. Here we provide evidence that Sp140 is a gene encoded within the Sst1 locus that represses type I IFN transcription during bacterial infections. We generated Sp140-/- mice and find they are susceptible to infection by Legionella pneumophila and Mycobacterium tuberculosis. Susceptibility of Sp140-/- mice to bacterial infection was rescued by crosses to mice lacking the type I IFN receptor (Ifnar-/-). Our results implicate Sp140 as an important negative regulator of type I IFNs that is essential for resistance to bacterial infections.

scholarly journals IFN-β signalling regulates RAW 264.7 macrophage activation, cytokine production, and killing activity

2019 ◽  
Vol 26 (3) ◽  
pp. 172-182
Author(s):  
Yalda Karimi ◽  
Elizabeth C Giles ◽  
Fatemeh Vahedi ◽  
Marianne V Chew ◽  
Tina Nham ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Critical Role ◽  
Raw 264.7 ◽  
Type I ◽  
Type I Ifn ◽  
Killing Activity ◽  
Raw 264.7 Macrophage

Type I IFN holds a critical role in host defence, providing protection against pathogenic organisms through coordinating a pro-inflammatory response. Type I IFN provides additional protection through mitigating this inflammatory response, preventing immunopathology. Within the context of viral infections, type I IFN signalling commonly results in successful viral clearance. Conversely, during bacterial infections, the role of type I IFN is less predictable, leading to either detrimental or beneficial outcomes. The factors responsible for the variability in the role of type I IFN remain unclear. Here, we aimed to elucidate differences in the effect of type I IFN signalling on macrophage functioning in the context of TLR activation. Using RAW 264.7 macrophages, we observed the influence of type I IFN to be dependent on the type of TLR ligand, length of TLR exposure and the timing of IFN-β signalling. However, in all conditions, IFN-β increased the production of the anti-inflammatory cytokine IL-10. Examination of RAW 264.7 macrophage function showed type I IFN to induce an activated phenotype by up-regulating MHC II expression and enhancing killing activity. Our results support a context-dependent role for type I IFN in regulating RAW 264.7 macrophage activity.

Uptake of collagen type I via macropinocytosis cause mTOR activation and anti-cancer drug resistance

2020 ◽  
Vol 526 (1) ◽  
pp. 191-198 ◽  
Author(s):  
Shota Yamazaki ◽  
Yinghan Su ◽  
Ami Maruyama ◽  
Hideki Makinoshima ◽  
Jun Suzuki ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Collagen Type ◽  
Collagen Type I ◽  
Cancer Drug ◽  
Type I ◽  
Cancer Drug Resistance ◽  
Anti Cancer

scholarly journals Actin Cytoskeleton Dynamics and Type I IFN-Mediated Immune Response: A Dangerous Liaison in Cancer?

Biology ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 913
Author(s):  
Paola Trono ◽  
Annalisa Tocci ◽  
Martina Musella ◽  
Antonella Sistigu ◽  
Paola Nisticò
Keyword(s):  
Immune Response ◽  
Actin Cytoskeleton ◽  
Cancer Treatment ◽  
Tissue Homeostasis ◽  
Type I ◽  
Type I Ifn ◽  
Anti Cancer ◽  
Complex Signaling ◽  
Cytoskeleton Dynamics

Chronic viral infection and cancer are closely inter-related and are both characterized by profound alteration of tissue homeostasis. The actin cytoskeleton dynamics highly participate in tissue homeostasis and act as a sensor leading to an immune-mediated anti-cancer and anti-viral response. Herein we highlight the crucial role of actin cytoskeleton dynamics in participating in a viral mimicry activation with profound effect in anti-tumor immune response. This still poorly explored field understands the cytoskeleton dynamics as a platform of complex signaling pathways which may regulate Type I IFN response in cancer. This emerging network needs to be elucidated to identify more effective anti-cancer strategies and to further advance the immuno-oncology field which has revolutionized the cancer treatment. For a progress to occur in this exciting arena we have to shed light on actin cytoskeleton related pathways and immune response. Herein we summarize the major findings, considering the double sword of the immune response and in particular the role of Type I IFN pathways in resistance to anti-cancer treatment.

scholarly journals Type I IFN Signaling Constrains IL-17A/F Secretion by γδ T Cells during Bacterial Infections

2010 ◽  
Vol 184 (7) ◽  
pp. 3755-3767 ◽  
Author(s):  
Thomas Henry ◽  
Girish S. Kirimanjeswara ◽  
Thomas Ruby ◽  
Jonathan W. Jones ◽  
Kaitian Peng ◽  
...  
Keyword(s):  
T Cells ◽  
Bacterial Infections ◽  
Γδ T Cells ◽  
Type I ◽  
Type I Ifn

scholarly journals Contribution of increased ISG15, ISGylation and deregulated type I IFN signaling in Usp18 mutant mice during the course of bacterial infections

2014 ◽  
Vol 15 (5) ◽  
pp. 282-292 ◽  
Author(s):  
S M Dauphinee ◽  
E Richer ◽  
M M Eva ◽  
F McIntosh ◽  
M Paquet ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Mutant Mice ◽  
Type I ◽  
Type I Ifn

scholarly journals Getting “Inside” Type I IFNs: Type I IFNs in Intracellular Bacterial Infections

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Deann T. Snyder ◽  
Jodi F. Hedges ◽  
Mark A. Jutila
Keyword(s):  
Host Cell ◽  
Legionella Pneumophila ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Type I Interferons ◽  
Intracellular Bacteria ◽  
Type I ◽  
Type I Ifn ◽  
Type I Ifns ◽  
Serovar Typhimurium

Type I interferons represent a unique and complex group of cytokines, serving many purposes during innate and adaptive immunity. Discovered in the context of viral infections, type I IFNs are now known to have myriad effects in infectious and autoimmune disease settings. Type I IFN signaling during bacterial infections is dependent on many factors including whether the infecting bacterium is intracellular or extracellular, as different signaling pathways are activated. As such, the repercussions of type I IFN induction can positively or negatively impact the disease outcome. This review focuses on type I IFN induction and downstream consequences during infection with the following intracellular bacteria:Chlamydia trachomatis,Listeria monocytogenes,Mycobacterium tuberculosis,Salmonella entericaserovar Typhimurium,Francisella tularensis,Brucella abortus,Legionella pneumophila, andCoxiella burnetii. Intracellular bacterial infections are unique because the bacteria must avoid, circumvent, and even co-opt microbial “sensing” mechanisms in order to reside and replicate within a host cell. Furthermore, life inside a host cell makes intracellular bacteria more difficult to target with antibiotics. Because type I IFNs are important immune effectors, modulating this pathway may improve disease outcomes. But first, it is critical to understand the context-dependent effects of the type I IFN pathway in intracellular bacterial infections.

scholarly journals Regnase-1 deficiency restrains Klebsiella pneumoniae infection by regulation of a Type I interferon response

2021 ◽  
Author(s):  
Giraldina Trevejo-Nunez ◽  
Li Fan ◽  
Becky Lin ◽  
Felix Aggor ◽  
Partha Biswas ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Bacterial Infections ◽  
Rna Binding ◽  
Inflammatory Responses ◽  
Defense Responses ◽  
Interferon Response ◽  
Type I ◽  
Type I Ifn ◽  
Autoimmune Inflammation ◽  
Acute Bacterial Infections

Excessive inflammatory responses can cause collateral tissue damage or autoimmune inflammation, sometimes with severe morbidity or mortality. During host defense responses, numerous negative feedback mechanisms are established to prevent excessive unchecked inflammation. However, this restraint can sometimes come at the cost of suboptimal infection control, and we do not fully understand how this balance is maintained during different infection settings. The endoribonuclease Regnase-1 (Reg1, Zc3h12a, MCPIP1) is an RNA binding protein (RBP) that binds and degrades many target mRNA transcripts. Reg1 is a potent feedback regulator of IL-17 and LPS signal transduction, among other stimuli. Consequently, Reg1 deficiency exacerbates autoimmune inflammation in multiple mouse models, but on the other hand, reduced Reg1 improves immunity to fungal infection. To date, the role of Reg1 in bacterial immunity is poorly defined. Here, we show that mice deficient in Reg1 are more resistant to pulmonary Klebsiella pneumoniae (KP) infection. Unexpectedly, effects of Reg1 deficiency were not due to accelerated eradication of bacteria or increased pro-inflammatory cytokine expression. Rather, alveolar macrophages from Reg1-deficient mice showed enrichment of Type I IFN-related genes upon KP infection, accompanied by increased Ifnb1 expression. Surprisingly, the stability of Ifnb1 mRNA was not altered by Reg1-deficiency; rather, mRNA encoding its upstream regulator IRF7 appeared to be a more prominent target. Thus, impaired Reg1 induces Type I IFN and enhances resistance to KP, raising the possibility that Reg1 could be a potential clinical target in acute bacterial infections.

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