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1.
《Cytokine & growth factor reviews》2014,25(6):631-639
The recognition of nucleic acids is a general strategy used by the host to detect invading pathogens. Many studies have established that MITA/STING is a central component in the innate immune response to cytosolic DNA and RNA derived from pathogens. MITA can act both as a direct sensor of cyclic dinucleotides (CDNs) and as an adaptor for the recruitment of downstream signaling components. In both roles, MITA is part of signaling cascades that orchestrate innate immune defenses against various pathogens, including viruses, bacteria and parasites. Here, we highlight recent studies that have uncovered the molecular mechanisms of MITA-mediated signal transduction and regulation, and discuss some notable issues that remain elusive. 相似文献
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《Cytokine & growth factor reviews》2014,25(6):657-668
Retroviruses can selectively trigger an array of innate immune responses through various PRR. The identification and the characterization of the molecular basis of retroviral DNA sensing by the DNA sensors IFI16 and cGAS has been one of the most exciting developments in viral immunology in recent years. DNA sensing by these cytosolic sensors not only leads to the initiation of the type I interferon (IFN) antiviral response and the induction of the inflammatory response, but also triggers cell death mechanisms including pyroptosis and apoptosis in retrovirus-infected cells, thereby providing important insights into the pathophysiology of chronic retroviral infection. Host restriction factors such as SAMHD1 and Trex1 play important roles in regulating innate immune sensing, and have led to the idea that innate immune defense and host restriction actually converge at different levels to determine the outcome of retroviral infection. In this review, we discuss the sensing of retroviruses by cytosolic DNA sensors, the relevance of host factors during retroviral infection, and the interplay between host factors and the innate antiviral response in different cell types, within the context of two human pathogenic retroviruses – human immunodeficiency virus (HIV-1) and human T cell-leukemia virus type I (HTLV-1). 相似文献
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The host takes use of pattern recognition receptors (PRRs) to defend against pathogen invasion or cellular damage. Among microorganism-associated molecular patterns detected by host PRRs, nucleic acids derived from bacteria or viruses are tightly supervised, providing a fundamental mechanism of host defense. Pathogenic DNAs are supposed to be detected by DNA sensors that induce the activation of NFκB or TBK1-IRF3 pathway. DNA sensor cGAS is widely expressed in innate immune cells and is a key sensor of invading DNAs in several cell types. cGAS binds to DNA, followed by a conformational change that allows the synthesis of cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) from adenosine triphosphate and guanosine triphosphate. cGAMP is a strong activator of STING that can activate IRF3 and subsequent type I interferon production. Here we describe recent progresses in DNA sensors especially cGAS in the innate immune responses against pathogenic DNAs. 相似文献
4.
Matteo Gentili Xavier Lahaye Francesca Nadalin Guilherme F.P. Nader Emilia Puig Lombardi Solène Herve Nilushi S. De Silva Derek C. Rookhuizen Elina Zueva Christel Goudot Mathieu Maurin Aurore Bochnakian Sebastian Amigorena Matthieu Piel Daniele Fachinetti Arturo Londoño-Vallejo Nicolas Manel 《Cell reports》2019,26(9):2377-2393.e13
5.
Lise Chauveau Anne Bridgeman Tiong K Tan Ryan Beveridge Joe N Frost Pramila Rijal Isabela Pedroza&#x;Pacheco Thomas Partridge Javier Gilbert&#x;Jaramillo Michael L Knight Xu Liu Rebecca A Russell Persephone Borrow Hal Drakesmith Alain R Townsend Jan Rehwinkel 《EMBO reports》2021,22(8)
Cyclic GMP‐AMP (cGAMP) is an immunostimulatory molecule produced by cGAS that activates STING. cGAMP is an adjuvant when administered alongside antigens. cGAMP is also incorporated into enveloped virus particles during budding. Here, we investigate whether inclusion of cGAMP within viral vaccine vectors enhances their immunogenicity. We immunise mice with virus‐like particles (VLPs) containing HIV‐1 Gag and the vesicular stomatitis virus envelope glycoprotein G (VSV‐G). cGAMP loading of VLPs augments CD4 and CD8 T‐cell responses. It also increases VLP‐ and VSV‐G‐specific antibody titres in a STING‐dependent manner and enhances virus neutralisation, accompanied by increased numbers of T follicular helper cells. Vaccination with cGAMP‐loaded VLPs containing haemagglutinin induces high titres of influenza A virus neutralising antibodies and confers protection upon virus challenge. This requires cGAMP inclusion within VLPs and is achieved at markedly reduced cGAMP doses. Similarly, cGAMP loading of VLPs containing the SARS‐CoV‐2 Spike protein enhances Spike‐specific antibody titres. cGAMP‐loaded VLPs are thus an attractive platform for vaccination. 相似文献
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7.
《Molecular cell》2023,83(9):1502-1518.e10
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8.
《Cell reports》2020,30(12):4096-4109.e5
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9.
《Advanced Biosystems》2017,1(1-2)
Overcoming the immunosuppressive tumor microenvironment (TME) is critical to realizing the potential of cancer immunotherapy strategies. Agonists of stimulator of interferon genes (STING), a cytosolic immune adaptor protein, have been shown to induce potent antitumor activity when delivered into the TME. However, the anionic properties of STING agonists make them poorly membrane permeable, and limit their ability to engage STING in the cytosol of responding cells. In this study, cationic liposomes with varying surface polyethylene glycol levels are used to encapsulate 2′3′ cyclic guanosine monophosphate‐adenosine monophosphate (cGAMP) to facilitate its cytosolic delivery. In vitro studies with antigen‐presenting cells (APCs) revealed that liposomal formulations substantially improve the cellular uptake of cGAMP and proinflammatory gene induction relative to free drug. Liposomal encapsulation allows cGAMP delivery to metastatic melanoma tumors in the lung, leading to antitumor activity, whereas free drug produces no effect at the same dose. Injection of liposomal cGAMP into orthotopic melanoma tumors shows retention of cGAMP at the tumor site and colocalization with tumor‐associated APCs. Liposomal delivery induces regression of injected tumors and produces immunological memory that protects previously treated mice from rechallenge with tumor cells. These results show that liposomal delivery improves STING agonist activity, and could improve their utility in clinical oncology. 相似文献
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Alexandre Dalet Philippe Pierre Alexandre Dalet Rafael J Argüello Alexis Combes Lionel Spinelli Sebastien Jaeger Mathieu Fallet Thien-Phong Vu Manh Andreia Mendes Jessica Perego Marisa Reverendo Voahirana Camosseto Marc Dalod Tobias Weil Manuel A Santos Evelina Gatti Philippe Pierre 《The EMBO journal》2017,36(6):761-782