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Manganese Increases the Sensitivity of the cGAS-STING Pathway for Double-Stranded DNA and Is Required for the Host Defense against DNA Viruses

The cGAS-STING pathway is required for host defense against DNA viruses. Wang et  al. find that upon virus infection, Manganese (Mn2+) is released from organelles into the cytosol and facilitates the activation of cGAS and STING. Their findings identify a role for Mn in innate immune activation and host anti-viral defense.
Source: Immunity - Category: Allergy & Immunology Authors: Tags: Article Source Type: research

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Preclinical and clinical studies have shown that viral-based immunotherapy has the potential to overcome resistance to immune checkpoint blockade (ICB) and to fill the unmet needs of many cancer patients. Poxviruses, such as modified vaccinia virus Ankara (MVA), have the potential as cancer immunotherapeutic agents. We recently showed that intratumoral (IT) delivery of inactivated modified vaccinia virus Ankara (iMVA) induces antitumor systemic immunity via the STING-mediated cytosolic DNA-sensing pathway and Batf3 –dependent CD103+/CD8+ dendritic cells (DCs).
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Adaptive and Auto-Immunity Source Type: research
Innate immunity is essential for the activation of adaptive immunity to defend the host from infections by other organisms. Altered innate immunity has been associated with skin inflammatory diseases such as psoriasis and atopic dermatitis (AD). Trim32 is a tripartite motif (TRIM) protein with innate antiviral activity mediated through STING and NF- κB signaling pathways. In our previous studies, we demonstrated that Trim32 protein level is high in psoriasis and low in AD skin. Further, we provided evidence that Trim32 deficiency contributes to enhanced TH2 immunity and compromised TH17 immunity in skin in response t...
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Innate Immunity, Microbiology, Inflammation Source Type: research
Keloids are exuberant scars in which overgrowths of fibrous tissue extend beyond the borders of the original skin injury. Traumatic insults that can lead to keloids include surgery, piercings, acne, insect bites, and even mild abrasions. These lesions do not regress, and can cause pain, pruritus and psychosocial effects when they appear. Pathway analysis of whole transcriptome data obtained from comparing RNA expression between matched keloid and normal tissue suggests that the PPAR γ signaling pathway may be dysregulated in keloids.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Skin of Color Source Type: research
Tumor-derived, cytosolic DNA has been reported to stimulate the production of type I interferon (IFN) through a STING-dependent signaling pathway in dendritic cells (DCs), which helps to initiate a spontaneous T cell response against melanoma. However, cytosolic DNA can also be recognized by AIM2, a cytosolic innate immune sensor, whose function in melanoma remains unclear. To determine the role of AIM2 in melanoma microenvironment, we subcutaneously challenged Aim2/ mice with B16F10 melanoma. Surprisingly, these mice exhibited a lower tumor burden with fewer tumor-infiltrating regulatory T cells (Tregs) than WT mice, indi...
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Pigmentation and Melanoma Source Type: research
Wound healing, a process of repair after skin injury can be divided into three phases: inflammatory phase, proliferative phase, and tissue remodeling. These steps are precisely regulated by a variety of mediators, such as cytokines and chemokines. Inflammatory phase, the first stage of wound healing, especially features an inflammatory reaction via these mediators. Recent reports demonstrated that cytoplasmic DNA-sensor cyclic GMP-AMP synthase (cGAS) activates the stimulator of interferon genes (STING) via production of cyclic GMP-AMP (cGAMP) and subsequently induces inflammatory cytokines including type interferon.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Tissue Regeneration and Wound Healing Source Type: research
We present 2 cases of scrub typhus with cholecystitis. The first patient is a 62 year old female who presented to the hospital with fever and body aches for 1 week and right upper quadrant abdominal pain for 3 days. She gave a history of an insect bite 2 weeks previously. She was diagnosed as having acute cholecystitis and underwent cholecystectomy. She continued with fever post-operatively and physical examination revealed an eschar. She had an immunofluorescence assay (IFA) performed that revealed a high IgM titer for Orientia tsutsugamushi. She was diagnosed as having scrub typhus, treated with doxycycline and she recov...
Source: Southeast Asian Journal of Tropical Medicine and Public Health - Category: Tropical Medicine Tags: Southeast Asian J Trop Med Public Health Source Type: research
In my newpolicy analysis released today, I identify 65 vetting failures where the visa vetting system allowed a foreign-born person to enter the United States as an adult or older teenager when they had already radicalized —80 percent occurred before 9/11. Just 13 vetting failures have occurred since 9/11, and only one—the last one (Tashfeen Malik)—resulted in any deaths in the United States. That’s one vetting failure for every 29 million visa or status approvals, and one deadly failure for every 379 million visa or status approvals from 2002 to 2016.As I note, 9/11 is reasonable point of analysis ...
Source: Cato-at-liberty - Category: American Health Authors: Source Type: blogs
Hymenoptera sting reactions are among life-threatening causes of allergy. Several epidemiology studies have assessed the risk of these kind of reactions, among the general population, around 3% of adults. This...
Source: Clinical and Molecular Allergy - Category: Allergy & Immunology Authors: Tags: Research Source Type: research
Abstract Stimulator of IFN genes (STING) is essential for the DNA-sensing innate immune pathway. Recently, evidence is emerging that suggests STING also plays important roles in autoimmunity, cancer therapy, and senescence. Although a multitude of post-translational modifications that regulate the STING pathway have been discovered, the cellular events that guide STING translocation remain unclear. Here, we show, paradoxically, that both BAPTA-AM-mediated calcium depletion and ionomycin-induced calcium elevation suppress STING translocation and STING-mediated IFN-β production. We demonstrate that the mitochon...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research
“With integrity, you have nothing to fear, since you have nothing to hide. With integrity, you will do the right thing, so you will have no guilt.” – Zig Ziglar When faced with deciding on how to act, sometimes the toughest part is figuring out how to do the right thing. Of course, how you view the right thing, what you think of as the right thing, makes all the difference. And this is often not clear. You may experience conflicting emotions, feel ambivalent about potential choices, or strongly for or against certain action — whether you are convinced that it either is or isn’t the right ...
Source: World of Psychology - Category: Psychiatry & Psychology Authors: Tags: Brain and Behavior Ethics & Morality Inspiration & Hope LifeHelper Motivation and Inspiration Self-Help Compassion Core Values Decision Making Pay It Forward Source Type: blogs
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