The Emerging Role of STING in Insect Innate Immune Responses and Pathogen Evasion Strategies

Liu, Qiu-Ning; Kausar, Saima; Tang, Ying-Yu; Huang, Weixin; Tang, Bo-Ping; Abbas, Muhammad Nadeem; Dai, Li-Shang

doi:10.3389/fimmu.2022.874605

Cited by 8 publications

(8 citation statements)

References 101 publications

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“…Cytosolic nucleic acid sensors serve as critical elements of innate immunity in many different organisms, reviewed in [ 86 ]. In mammalian cells, two of the aforementioned SMA modifiers (CORO1C and ZPR1) have been implicated in R-loop resolution and the subsequent DNA-damage response [ 87 – 89 ], both of which fall into the general category of DAMPs.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of innate immune signaling in animal models of spinal muscular atrophy

Garcia,

Steiner,

Raimer

et al. 2024

BMC Biol

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Background Spinal muscular atrophy (SMA) is a devastating neuromuscular disease caused by hypomorphic loss of function in the survival motor neuron (SMN) protein. SMA presents across a broad spectrum of disease severity. Unfortunately, genetic models of intermediate SMA have been difficult to generate in vertebrates and are thus unable to address key aspects of disease etiology. To address these issues, we developed a Drosophila model system that recapitulates the full range of SMA severity, allowing studies of pre-onset biology as well as late-stage disease processes. Results Here, we carried out transcriptomic and proteomic profiling of mild and intermediate Drosophila models of SMA to elucidate molecules and pathways that contribute to the disease. Using this approach, we elaborated a role for the SMN complex in the regulation of innate immune signaling. We find that mutation or tissue-specific depletion of SMN induces hyperactivation of the immune deficiency (IMD) and Toll pathways, leading to overexpression of antimicrobial peptides (AMPs) and ectopic formation of melanotic masses in the absence of an external challenge. Furthermore, the knockdown of downstream targets of these signaling pathways reduced melanotic mass formation caused by SMN loss. Importantly, we identify SMN as a negative regulator of a ubiquitylation complex that includes Traf6, Bendless, and Diap2 and plays a pivotal role in several signaling networks. Conclusions In alignment with recent research on other neurodegenerative diseases, these findings suggest that hyperactivation of innate immunity contributes to SMA pathology. This work not only provides compelling evidence that hyperactive innate immune signaling is a primary effect of SMN depletion, but it also suggests that the SMN complex plays a regulatory role in this process in vivo. In summary, immune dysfunction in SMA is a consequence of reduced SMN levels and is driven by cellular and molecular mechanisms that are conserved between insects and mammals.

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Section: Discussionmentioning

confidence: 99%

Dysregulation of innate immune signaling in animal models of spinal muscular atrophy

Garcia,

Steiner,

Raimer

et al. 2024

BMC Biol

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“…Gliomas reside in the brain and were previously thought to be immunologically privileged and immune surveillance spared, but recent studies have shown that the brain is an active regulatory point of immune surveillance. 57,60 Without disruption of the BBB, the infiltration of peripheral immune cells into gliomas is very limited. However, when the BBB is disrupted by tumor growth or inflammation, gliomas are infiltrated by immunosuppressive cells.…”

Section: Mechanisms Of Chemotherapy Resistance In Gliomamentioning

confidence: 99%

Nanoparticles for efficient drug delivery and drug resistance in glioma: New perspectives

Liu,

Yang,

et al. 2024

CNS Neurosci Ther

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Gliomas are the most common primary tumors of the central nervous system, with glioblastoma multiforme (GBM) having the highest incidence, and their therapeutic efficacy depends primarily on the extent of surgical resection and the efficacy of postoperative chemotherapy. The role of the intracranial blood–brain barrier and the occurrence of the drug‐resistant gene O6‐methylguanine‐DNA methyltransferase have greatly limited the efficacy of chemotherapeutic agents in patients with GBM and made it difficult to achieve the expected clinical response. In recent years, the rapid development of nanotechnology has brought new hope for the treatment of tumors. Nanoparticles (NPs) have shown great potential in tumor therapy due to their unique properties such as light, heat, electromagnetic effects, and passive targeting. Furthermore, NPs can effectively load chemotherapeutic drugs, significantly reduce the side effects of chemotherapeutic drugs, and improve chemotherapeutic efficacy, showing great potential in the chemotherapy of glioma. In this article, we reviewed the mechanisms of glioma drug resistance, the physicochemical properties of NPs, and recent advances in NPs in glioma chemotherapy resistance. We aimed to provide new perspectives on the clinical treatment of glioma.

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“…Researchers have been able to identify novel circRNAs by revising or discovering existing ones in recent years as the depth of sequencing platforms has increased. CircRNAs of insects are involved in various aspects of insect biology, including development [ 63 ], reproduction [ 64 , 65 ], metamorphosis [ 66 , 67 ], insecticide resistance, aging [ 68 ], life-span [ 69 ], and host–pathogen interactions and immunity [ 70 , 71 ], among others ( Figure 2 ). These potential functions imply that they could be key regulators of insect physiological functions.…”

Section: Circrnas In Insectsmentioning

confidence: 99%

The Potential Biological Roles of Circular RNAs in the Immune Systems of Insects to Pathogen Invasion

Abbas

Kausar

Gul

et al. 2023

Genes

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Circular RNAs (circRNAs) are a newly discovered class of endogenously expressed non-coding RNAs (ncRNAs). They are highly stable, covalently closed molecules that frequently exhibit tissue-specific expression in eukaryotes. A small number of circRNAs are abundant and have been remarkably conserved throughout evolution. Numerous circRNAs are known to play important biological roles by acting as microRNAs (miRNAs) or protein inhibitors (‘sponges’), by regulating the function of proteins, or by being translated themselves. CircRNAs have distinct cellular functions due to structural and production differences from mRNAs. Recent advances highlight the importance of characterizing circRNAs and their targets in a variety of insect species in order to fully understand how they contribute to the immune responses of these insects. Here, we focus on the recent advances in our understanding of the biogenesis of circRNAs, regulation of their abundance, and biological roles, such as serving as templates for translation and in the regulation of signaling pathways. We also discuss the emerging roles of circRNAs in regulating immune responses to various microbial pathogens. Furthermore, we describe the functions of circRNAs encoded by microbial pathogens that play in their hosts.

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The Emerging Role of STING in Insect Innate Immune Responses and Pathogen Evasion Strategies

Cited by 8 publications

References 101 publications

Dysregulation of innate immune signaling in animal models of spinal muscular atrophy

Dysregulation of innate immune signaling in animal models of spinal muscular atrophy

Nanoparticles for efficient drug delivery and drug resistance in glioma: New perspectives

The Potential Biological Roles of Circular RNAs in the Immune Systems of Insects to Pathogen Invasion

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