STING-dependent autophagy suppresses Nosema bombycis infection in silkworms, Bombyx mori

Hua, Xiaoting; Xü, Wei; Ma, Sanyuan; Xia, Qingyou

doi:10.1016/j.dci.2020.103862

Cited by 18 publications

(10 citation statements)

References 28 publications

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“…During the early stage of sepsis, autophagy protects the host from MODS by preventing the death of immune cells, maintaining homeostasis between the production of pro- and anti-inflammatory cytokines, and eliminating microbial infection [ 21 ]. A vast number of studies have uncovered the mechanism of STING-induced autophagy for the elimination of intracellular microorganisms and subcellular organelles [ 22 ]. cGAS-STING-mediated autophagy is also known to be indispensable for removing cytosolic DNA and inflammatory signaling factors to restrict the inflammatory response raised by the pathway itself under physiological or compensable disease conditions [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Circulating mitochondrial DNA-triggered autophagy dysfunction via STING underlies sepsis-related acute lung injury

Liu

Zhang

et al. 2021

Cell Death Dis

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The STING pathway and its induction of autophagy initiate a potent immune defense response upon the recognition of pathogenic DNA. However, this protective response is minimal, as STING activation worsens organ damage, and abnormal autophagy is observed during progressive sepsis. Whether and how the STING pathway affects autophagic flux during sepsis-induced acute lung injury (sALI) are currently unknown. Here, we demonstrate that the level of circulating mtDNA and degree of STING activation are increased in sALI patients. Furthermore, STING activation was found to play a pivotal role in mtDNA-mediated lung injury by evoking an inflammatory storm and disturbing autophagy. Mechanistically, STING activation interferes with lysosomal acidification in an interferon (IFN)-dependent manner without affecting autophagosome biogenesis or fusion, aggravating sepsis. Induction of autophagy or STING deficiency alleviated lung injury. These findings provide new insights into the role of STING in the regulatory mechanisms behind extrapulmonary sALI.

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Section: Discussionmentioning

confidence: 99%

Circulating mitochondrial DNA-triggered autophagy dysfunction via STING underlies sepsis-related acute lung injury

Liu

Zhang

et al. 2021

Cell Death Dis

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“…Upon infection, innate immune responses of silkworms Insects 2021, 12, 799 2 of 13 against the pathogen N. bombycis are activated, such as hemocytin [16] and Bombyx Turtle protein expression [17]. Moreover, the autophagy pathway is induced by N. bombycis infection [18,19], and apoptosis and reactive oxygen species production also change upon infection with N. bombycis [20].…”

Section: Introductionmentioning

confidence: 99%

UDP-Glucosyltransferases Induced by Nosema bombycis Provide Resistance to Microsporidia in Silkworm (Bombyx mori)

Yang

Wei

et al. 2021

Insects

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As a silkworm pathogen, the microsporidian N. bombycis can be transovarially transmitted from parent to offspring and seriously impedes sericulture industry development. Previous studies found that Uridine diphosphate (UDP)-glycosyltransferases (UGTs) are involved in regulating diverse cellular processes, such as detoxification, pigmentation, and odorant sensing. Our results showed that BmUGT10295 and BmUGT8453 genes were specifically induced in infected silkworms, but other BmUGTs were not. Tissue distribution analysis of the two BmUGTs showed that the transcriptions of the two BmUGTs were mainly activated in the midgut and Malpighian tubule of infected silkworms. Furthermore, there were significantly fewer microsporidia in over-expressed BmUGTs compared with the control, but there were significantly more microsporidia in RNA interference BmUGTs compared with the control. These findings indicate that the two BmUGTs were induced by N. bombycis and provided resistance to the microsporidia.

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“…Remarkably, CDN to STING signaling seems to have originated in bacteria, in which it may be important in bacteriophage defense (28,29). Studies on the function of STING in animals that lack type I IFN have been mostly limited to insects, in which STING seems to be protective during viral (30)(31)(32)(33), bacterial (34), and microsporidial (35) infection. In insects, STING may promote defense through activation of autophagy (32,35) and/or induction of NF-κB-dependent defense genes (30,31,34).…”

mentioning

confidence: 99%

“…Studies on the function of STING in animals that lack type I IFN have been mostly limited to insects, in which STING seems to be protective during viral (30)(31)(32)(33), bacterial (34), and microsporidial (35) infection. In insects, STING may promote defense through activation of autophagy (32,35) and/or induction of NF-κB-dependent defense genes (30,31,34). Most ISGs are lacking from insect genomes and are not induced by CDN-STING signaling (31).…”

mentioning

confidence: 99%

The cyclic dinucleotide 2′3′-cGAMP induces a broad antibacterial and antiviral response in the sea anemone Nematostella vectensis

Margolis

Dietzen

Hayes

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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In mammals, cyclic dinucleotides (CDNs) bind and activate STING to initiate an antiviral type I interferon response. CDNs and STING originated in bacteria and are present in most animals. By contrast, interferons are believed to have emerged in vertebrates; thus, the function of CDN signaling in invertebrates is unclear. Here, we use a CDN, 2′3′ cyclic guanosine monophosphate-adenosine monophosphate (2′3′-cGAMP), to activate immune responses in a model cnidarian invertebrate, the starlet sea anemone Nematostella vectensis. Using RNA sequencing, we found that 2′3′-cGAMP induces robust transcription of both antiviral and antibacterial genes in N. vectensis. Many of the antiviral genes induced by 2′3′-cGAMP are homologs of vertebrate interferon-stimulated genes, implying that the interferon response predates the evolution of interferons. Knockdown experiments identified a role for NF-κB in specifically inducing antibacterial genes downstream of 2′3′-cGAMP. Some of these putative antibacterial genes were also found to be induced during Pseudomonas aeruginosa infection. We characterized the protein product of one of the putative antibacterial genes, the N. vectensis homolog of Dae4, and found that it has conserved antibacterial activity. This work suggests that a broad antibacterial and antiviral transcriptional response is an evolutionarily ancestral output of 2′3′-cGAMP signaling in animals.

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STING-dependent autophagy suppresses Nosema bombycis infection in silkworms, Bombyx mori

Cited by 18 publications

References 28 publications

Circulating mitochondrial DNA-triggered autophagy dysfunction via STING underlies sepsis-related acute lung injury

Circulating mitochondrial DNA-triggered autophagy dysfunction via STING underlies sepsis-related acute lung injury

UDP-Glucosyltransferases Induced by Nosema bombycis Provide Resistance to Microsporidia in Silkworm (Bombyx mori)

The cyclic dinucleotide 2′3′-cGAMP induces a broad antibacterial and antiviral response in the sea anemone Nematostella vectensis

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