Function and Regulation of Nuclear DNA Sensors During Viral Infection and Tumorigenesis

Zhang, Fan; Yuan, Yi; Ma, Feng

doi:10.3389/fimmu.2020.624556

Cited by 19 publications

(15 citation statements)

References 111 publications

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“…PRRs include mainly Toll-like receptors (TLR) (10), NOD-like receptors (NLRs) (11), C-type lectin receptors (CLRs) (12), RIG-I-like receptors (RLRs) (13), and DNA receptors/sensors (14). Among these, DAI (15), IFI16 (16,17), DDX41 (18), MRE11 (19), LSm14A (20), DHX9 (21), hnRNPA2B1 (22), and cGAS (23)(24)(25) are considered DNA receptors/sensors. cGAS is a cytoplasmic nucleic acid sensor with the widest recognition ability for double-stranded DNA (dsDNA); it binds dsDNA in a manner independent of sequence specificity (23).…”

Section: Introductionmentioning

confidence: 99%

A Variety of Nucleic Acid Species Are Sensed by cGAS, Implications for Its Diverse Functions

et al. 2022

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Cyclic GMP-AMP synthase (cGAS) recognizes double-stranded DNA (dsDNA) derived from invading pathogens and induces an interferon response via activation of the key downstream adaptor protein stimulator of interferon genes (STING). This is the most classic biological function of the cGAS-STING signaling pathway and is critical for preventing pathogenic microorganism invasion. In addition, cGAS can interact with various types of nucleic acids, including cDNA, DNA : RNA hybrids, and circular RNA, to contribute to a diverse set of biological functions. An increasing number of studies have revealed an important relationship between the cGAS-STING signaling pathway and autophagy, cellular senescence, antitumor immunity, inflammation, and autoimmune diseases. This review details the mechanism of action of cGAS as it interacts with different types of nucleic acids, its rich biological functions, and the potential for targeting this pathway to treat various diseases.

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Section: Introductionmentioning

confidence: 99%

A Variety of Nucleic Acid Species Are Sensed by cGAS, Implications for Its Diverse Functions

et al. 2022

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“…Although initially enigmatic, in recent years, a plethora of potential nuclear sensors of foreign DNA were identified, including cGAS, IFI16, hnRNPA2B1, DA/ZBP1, TLR7/9, ZCCHC3, RNA Pol III, etc. [ 54 ]. Among them, for cGAS (recognition of DNA double-strand breaks), IFI16 (functions as a transcriptional repressor of foreign DNA), and hnRNPA2B1 (activates and amplifies antiviral response), DNA-sensing activity was directly determined ( Figure 1 B).…”

Section: The Role Of Innate Immunity In Restricting Viral Replicationmentioning

confidence: 99%

“…Among them, for cGAS (recognition of DNA double-strand breaks), IFI16 (functions as a transcriptional repressor of foreign DNA), and hnRNPA2B1 (activates and amplifies antiviral response), DNA-sensing activity was directly determined ( Figure 1 B). More detailed information about the functioning of nuclear DNA sensors can be found in recent reviews [ 54 ].…”

Section: The Role Of Innate Immunity In Restricting Viral Replicationmentioning

confidence: 99%

Immunity and Viral Infections: Modulating Antiviral Response via CRISPR–Cas Systems

Brezgin

Kostyusheva

Bayurova

et al. 2021

Viruses

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Viral infections cause a variety of acute and chronic human diseases, sometimes resulting in small local outbreaks, or in some cases spreading across the globe and leading to global pandemics. Understanding and exploiting virus–host interactions is instrumental for identifying host factors involved in viral replication, developing effective antiviral agents, and mitigating the severity of virus-borne infectious diseases. The diversity of CRISPR systems and CRISPR-based tools enables the specific modulation of innate immune responses and has contributed impressively to the fields of virology and immunology in a very short time. In this review, we describe the most recent advances in the use of CRISPR systems for basic and translational studies of virus–host interactions.

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“…On the other hand, recent studies highlight that the nucleus is an innate recognition site for cGAS-STING activation. [17][18][19] Currently, this pathway and the resultant type I interferon are intensively studied to improve antitumor immunotherapy. 20,21 Therefore, we ask whether the lysosomal-nuclear machinery can be explored to fully arouse the antitumor activity of macrophages by targeting both lysosomal pH and the nuclear innate immunity.…”

Section: Introductionmentioning

confidence: 99%

Chemo-drugs in cell microparticles reset antitumor activity of macrophages by activating lysosomal P450 and nuclear hnRNPA2B1

Wei

Zhang

Yang

et al. 2023

Sig Transduct Target Ther

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Macrophages in tumors (tumor-associated macrophages, TAMs), a major population within most tumors, play key homeostatic functions by stimulating angiogenesis, enhancing tumor cell growth, and suppressing antitumor immunity. Resetting TAMs by simple, efficacious and safe approach(s) is highly desirable to enhance antitumor immunity and attenuate tumor cell malignancy. Previously, we used tumor cell-derived microparticles to package chemotherapeutic drugs (drug-MPs), which resulted in a significant treatment outcome in human malignant pleural effusions via neutrophil recruitments, implicating that drug-MPs might reset TAMs, considering the inhibitory effects of M2 macrophages on neutrophil recruitment and activation. Here, we show that drug-MPs can function as an antitumor immunomodulator by resetting TAMs with M1 phenotype and IFN-β release. Mechanistically, drug molecules in tumor MPs activate macrophage lysosomal P450 monooxygenases, resulting in superoxide anion formation, which further amplifies lysosomal ROS production and pH value by activating lysosomal NOX2. Consequently, lysosomal Ca2+ signaling is activated, thus polarizing macrophages towards M1. Meanwhile, the drug molecules are delivered from lysosomes into the nucleus where they activate DNA sensor hnRNPA2B1 for IFN-β production. This lysosomal-nuclear machinery fully arouses the antitumor activity of macrophages by targeting both lysosomal pH and the nuclear innate immunity. These findings highlight that drug-MPs can act as a new immunotherapeutic approach by revitalizing antitumor activity of macrophages. This mechanistic elucidation can be translated to treat malignant ascites by drug-MPs combined with PD-1 blockade.

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Function and Regulation of Nuclear DNA Sensors During Viral Infection and Tumorigenesis

Cited by 19 publications

References 111 publications

A Variety of Nucleic Acid Species Are Sensed by cGAS, Implications for Its Diverse Functions

A Variety of Nucleic Acid Species Are Sensed by cGAS, Implications for Its Diverse Functions

Immunity and Viral Infections: Modulating Antiviral Response via CRISPR–Cas Systems

Chemo-drugs in cell microparticles reset antitumor activity of macrophages by activating lysosomal P450 and nuclear hnRNPA2B1

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