Create accountLogin

Recent searches

No recent searches

Search options

Only available when logged in.
med-mastodon.com is one of the many independent Mastodon servers you can use to participate in the fediverse.
Medical community on Mastodon

Administered by:

Server stats:

408
active users

med-mastodon.com: AboutProfiles directoryPrivacy policy

Mastodon: AboutGet the appKeyboard shortcutsView source codev4.3.8

#Interferon

0 posts0 participants0 posts today
Public
Auscandoc

Human challenge uncovers local and systemic response dynamics | Nature nature.com/articles/s41586-024 “observed that the response in blood preceded the nasopharyngeal response. Moreover, immune infiltration occurred early in samples from individuals with only transient infection and later in samples from individuals with sustained infection. High expression of before inoculation was associated with preventing sustained infection”

NatureHuman SARS-CoV-2 challenge uncovers local and systemic response dynamics - NatureA human SARS-CoV-2 challenge study in individuals without previous exposure to the virus or vaccines provides detailed profiles of local and systemic epithelial and immune cell response dynamics over time and infection status.
Public
Thiago Carvalho

'Here we examine the contribution of Mitogen Activated Protein Kinase (MAPK) signaling on IFNλ-mediated antiviral activity. We find that extracellular-signal-regulated kinase 5 (ERK5), a poorly characterized member of the conventional MAPK family, potentiates the antiviral efficacy of IFNλ.'
#Preprint #Immunology #InnateImmunity #Interferon

biorxiv.org/content/10.1101/20

bioRxiv · ERK5 Signaling is Required for Type III IFN-mediated Mucosal Antiviral ResponsesType III interferons (IFNλ) are innate immune cytokines that limit viral replication and coordinate tissue repair through the induction of interferon stimulated genes (ISGs). This response must be tightly regulated to avoid excessive responses that result in the disruption of tissue barrier integrity or inefficient responses that allow for pathogen escape. Here we examine the contribution of Mitogen Activated Protein Kinase (MAPK) signaling on IFNλ-mediated antiviral activity. We find that extracellular-signal-regulated kinase 5 (ERK5), a poorly characterized member of the conventional MAPK family, potentiates the antiviral efficacy of IFNλ. Chemical inhibition and genetic targeting of ERK5 during IFNλ treatment of cells results in a decrease in ISG induction and impaired control of viral infections. This decrease in IFNλ antiviral efficacy in the absence of ERK5 kinase activity corresponded to lowered STAT1 phosphorylation, revealing a noncanonical role for ERK5 in STAT1 activation downstream of IFNλ. In contrast, type I IFN antiviral signaling is largely resistant to ERK5 modulation. Altogether, we identify ERK5 as a potentiator of STAT1 activation, ISG expression, and antiviral activity following type III IFN stimulation. ### Competing Interest Statement The authors have declared no competing interest.
Public
Thiago Carvalho

"Repurposing generic medicine has the potential to bring new treatments for infectious diseases to patients efficiently and equitably. In this study, we found that intranasal delivery of neomycin, a generic aminoglycoside antibiotic, induces the expression of interferon-stimulated genes (ISGs) in the nasal mucosa that is independent of the commensal microbiota."
Mao, Akiko Iwasaki et al
#Immunology #Interferon

pnas.org/doi/10.1073/pnas.2319

Public
Zoomers of the Sunshine Coast

How much we still don’t understand about our immune system… COVID-19 researchers discover hidden natural immune defence pathway

They detected 10 new compounds made by the body in response to the SARS Cov-2 virus.

VIPERIN—short for virus inhibitory protein, endoplasmic reticulum-associated, interferon-inducible—is a multifunctional, interferon-inducible protein that regulates virus replication.

#interferon #VIPERIN

pubs.acs.org/doi/10.1021/acs.j

medicalxpress.com/news/2024-02

Continued thread
Public
Rhyothemis

from ⬆️ "These nettles are renowned for inflicting extremely painful stings that are characterized by acute electric shocklike, piercing, pricking and burning sensations lasting for many hours, followed by intermittent painful flares and allodynia that persists for days or even weeks."

Similarities to other types of neuropathic pain, including small fiber neuropathy and Long Covid associated neuropathy.

~

"These results provide important insights into the function of NaV channels in sensory neurons, identify TMEM233 as a previously unknown NaV1.7interacting protein, and describe the dispanins as bifunctional proteins that cause allosteric changes in channel gating upon binding of pain causing venom peptides."

~

Not finding much on TMEM233. Some dispanins are interferon activated.

review article from 2012:
- The Dispanins: A Novel Gene Family of Ancient Origin That Contains 14 Human Members
doi.org/10.1371%2Fjournal.pone

"The IFITM1–3 proteins were identified 25 years ago as being upregulated by interferons (IFN) [6]. Recently they received considerable attentions as IFITM1–3 were found to prevent infection of a growing list of viruses such as HIV-1, SARS influenza A H1N1, West Nile and Dengue fever viruses [7], [8], [9], [10]. Hence, proteins of the IFITM family mediate part of the antiviral response orchestrated by IFNs. However, the IFITM family is also involved in other processes such as oncogenesis, bone mineralization (IFITM5) and germ cell development (IFITM1 and 3) and IFITM5 has not been identified as interferon-inducible [11], [12], [13], [14]. Although the biological roles of the IFITM genes are emerging, no thorough evolutionary analysis has been performed on this group.

In this study, we sought to infer the evolutionary history of the human IFITM genes and identify potential homologues. We mined 36 eukaryotic species, covering all major eukaryotic groups, and found that the IFITMs form a subfamily in a larger novel family that has ten human members in addition to the four IFITM genes. We propose Dispanins as a novel name for this family, which refers to their common 2TM structure. "

journals.plos.orgThe Dispanins: A Novel Gene Family of Ancient Origin That Contains 14 Human MembersThe Interferon induced transmembrane proteins (IFITM) are a family of transmembrane proteins that is known to inhibit cell invasion of viruses such as HIV-1 and influenza. We show that the IFITM genes are a subfamily in a larger family of transmembrane (TM) proteins that we call Dispanins, which refers to a common 2TM structure. We mined the Dispanins in 36 eukaryotic species, covering all major eukaryotic groups, and investigated their evolutionary history using Bayesian and maximum likelihood approaches to infer a phylogenetic tree. We identified ten human genes that together with the known IFITM genes form the Dispanin family. We show that the Dispanins first emerged in eukaryotes in a common ancestor of choanoflagellates and metazoa, and that the family later expanded in vertebrates where it forms four subfamilies (A–D). Interestingly, we also find that the family is found in several different phyla of bacteria and propose that it was horizontally transferred to eukaryotes from bacteria in the common ancestor of choanoflagellates and metazoa. The bacterial and eukaryotic sequences have a considerably conserved protein structure. In conclusion, we introduce a novel family, the Dispanins, together with a nomenclature based on the evolutionary origin.
#TMEM233#dispanins#IFITM
Public *
halama_immuno

#innateimmunity in action: #immunotherapy against #breastcancer with TLR3 ligand and interferon alpha. Only six patients in this #trial , but biopsy analyses show improved #inmuneinfiltration with #TILs and is linked to clinical observations. #interferon #cytokines #immunology #macrophages @chfloudas
jitc.bmj.com/content/11/11/e00

Journal for ImmunoTherapy of Cancer · Systemic infusion of TLR3-ligand and IFN-α in patients with breast cancer reprograms local tumor microenvironments for selective CTL influxBackground Presence of cytotoxic T lymphocytes (CTL) in the tumor microenvironment (TME) predicts the effectiveness of cancer immunotherapies. The ability of toll-like receptor 3 (TLR3) ligands, interferons (IFNs) and COX2 inhibitors to synergistically induce CTL-attracting chemokines (but not regulatory T cell (Treg)-attractants) in the TME, but not in healthy tissues, observed in our preclinical studies, suggested that their systemic application can reprogram local TMEs. Methods Six evaluable patients (33–69 years) with metastatic triple-negative breast cancer received six doses of systemic chemokine-modulating (CKM) regimen composed of TLR3 ligand (rintatolimod; 200 mg; intravenous), IFN-α2b (20 MU/m2; intravenous) and COX2 inhibitor (celecoxib; 2×200 mg; oral) over 2 weeks. The predetermined primary endpoint was the intratumoral change in the expression of CTL marker, CD8α, in the post-CKM versus pre-CKM tumor biopsies. Patients received follow-up pembrolizumab (200 mg, intravenously, every 3 weeks), starting 3–8 days after completion of CKM. Results Post-CKM biopsies showed selectively increased CTL markers CD8α (average 10.2-fold, median 5.5-fold, p=0.034) and granzyme B (GZMB; 6.1-fold, median 5.8-fold, p=0.02), but not FOXP3 (Treg marker) relative to HPRT1 expression, resulting in the increases in average CD8α/FOXP3 ratio and GZMB/FOXP3 ratio. CKM increased intratumoral CTL-attractants CCL5 and CXCL10, but not Treg-attractants CCL22 or CXCL12. In contrast, CD8+ T cells and their CXCR3+ subset showed transient decreases in blood. One clinical response (breast tumor autoamputation) and three stable diseases were observed. The patient with clinical response remains disease free, with a follow-up of 46 months as of data cut-off. Conclusions Short-term systemic CKM selectively increases CTL numbers and CTL/Treg ratios in the TME, while transiently decreasing CTL numbers in the blood. Transient effects of CKM suggest that its simultaneous application with checkpoint blockade and other forms of immunotherapy may be needed for optimal outcomes. All data relevant to the study are included in the article or uploaded as supplementary information.
Public
Scientific Frontline

Researchers found that #interferon-gamma signaling caused hyperactivation of ERK in human #melanoma cell lines. The #ERK protein, when hyperactive, causes stress in the #cell, and this stress ultimately leads to cell death through specific proteins called #DR5 and #NOXA
#Cancer #Medical #sflorg
sflorg.com/2023/10/med10102301

www.sflorg.comScientists identify new pathway activated by interferon-gamma that leads to tumor cell deathA new role for a protein called extracellular signal-regulated kinase (ERK)
Public
Thiago Carvalho

Now I cant stop singing "more than a spike gene" to the tune of the BeeGees (protein didnt fit the meter).

'We assessed the role of ORF6 during infection using recombinant viruses carrying a deletion or loss-of-function (LoF) mutation in ORF6. ORF6 plays key roles in interferon antagonism and viral pathogenesis by interfering with nuclear import and specifically the translocation of IRF and STAT transcription factors.'
#Covid #Covid19 #SarsCov2 #Interferon #Virology #Immunology #InnateImmunity

sciencedirect.com/science/arti

Public *
Victoria Stuart 🇨🇦 🏳️‍⚧️

Aging Brain: Is Misplaced DNA to Blame?
science.org/content/blog-post/
Discussion: news.ycombinator.com/item?id=3

Comment: aging is ubiquitous, stochastic, multifactorial, physiochemical, innate (cell/molecular biology), with environmental factors. Intimately related to disease, including cancer.
That said, any insight contributes to understanding. 👍️

#ageing#aging#DNA
Public
TheBinderLab

Finally, it’s out! I must say, I am really, really fond of this paper– if you are into #innateimmunity, the #antiviralresponse and #interferon, I think you may enjoy reading it:

life-science-alliance.org/cont

Nothing spectacularly new, but very comprehensive characterization of the #RIGI and #IFN pathway!

Life Science AllianceHigh-resolution kinetic characterization of the RIG-I-signaling pathway and the antiviral responseRIG-I recognizes viral dsRNA and activates a cell-autonomous antiviral response. Upon stimulation, it triggers a signaling cascade leading to the production of type I and III IFNs. IFNs are secreted and signal to elicit the expression of IFN-stimulated genes, establishing an antiviral state of the cell. The topology of this pathway has been studied intensively, however, its exact dynamics are less understood. Here, we employed electroporation to synchronously activate RIG-I, enabling us to characterize cell-intrinsic innate immune signaling at a high temporal resolution. Employing IFNAR1/IFNLR-deficient cells, we could differentiate primary RIG-I signaling from secondary signaling downstream of the IFN receptors. Based on these data, we developed a comprehensive mathematical model capable of simulating signaling downstream of dsRNA recognition by RIG-I and the feedback and signal amplification by IFN. We further investigated the impact of viral antagonists on signaling dynamics. Our work provides a comprehensive insight into the signaling events that occur early upon virus infection and opens new avenues to study and disentangle the complexity of the host–virus interface.
ExploreLive feeds
About