Intracellular bacteria engage a STING–TBK1–MVB12b pathway to enable paracrine cGAS–STING signalling

Nandakumar, Ramya; Tschismarov, Roland; Meissner, Felix; Prabakaran, Thaneas; Krissanaprasit, Abhichart; Farahani, Ensieh; Zhang, Bao‐cun; Assil, Sonia; Martin, Amandine; Bertrams, Wilhelm; Holm, Christian K.; Ablasser, Andrea; Klause, Tanja; Thomsen, Martin K.; Schmeck, Bernd; Howard, Kenneth A.; Henry, Thomas; Gothelf, Kurt V.; Decker, Thomas; Paludan, Søren R.

doi:10.1038/s41564-019-0367-z

Cited by 108 publications

(104 citation statements)

References 54 publications

Supporting

Mentioning

100

Contrasting

Unclassified

Order By: Relevance

“…Yersinia outer protein J (YopJ) deubiquitinates STING and impedes the formation of the STING signalosome (160). The cGAS-STING pathway activation even impedes the elimination of Listeria monocytogenes because bacterial DNA can be packaged into EVs and transferred into T cells, where it induces apoptosis of T cells (161,162).…”

Section: Cgas-sting Pathway In Infectionmentioning

confidence: 99%

Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response

2020

View full text Add to dashboard Cite

Double-stranded DNA (dsDNA) sensor cyclic-GMP-AMP synthase (cGAS) along with the downstream stimulator of interferon genes (STING) acting as essential immunesurveillance mediators have become hot topics of research. The intrinsic function of the cGAS-STING pathway facilitates type-I interferon (IFN) inflammatory signaling responses and other cellular processes such as autophagy, cell survival, senescence. cGAS-STING pathway interplays with other innate immune pathways, by which it participates in regulating infection, inflammatory disease, and cancer. The therapeutic approaches targeting this pathway show promise for future translation into clinical applications. Here, we present a review of the important previous works and recent advances regarding the cGAS-STING pathway, and provide a comprehensive understanding of the modulatory pattern of the cGAS-STING pathway under multifarious pathologic states.

show abstract

Section: Cgas-sting Pathway In Infectionmentioning

confidence: 99%

Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response

2020

View full text Add to dashboard Cite

show abstract

“…Beyond CDNs, bacterial DNA resulting from bacteriolysis of Listeria monocytogenes 205 is able to induce IFNβ expression dependent on the cGAS‐, STING‐, and IFI16‐related pathways. Interestingly, Listeria DNA from infected cells can be sorted into extracellular vesicles and delivered to bystander cells to stimulate the cGAS‐STING signaling, a process mediated by the multivesicular body protein MVB12b 206 . The mechanism of how cGAS senses the nucleic acid products from other pathogenic and commensal bacteria and how bacteria exploit this pathway to evade immune surveillance remains to be further determined.…”

Section: Cgas and Stingmentioning

confidence: 99%

The microbiome and cytosolic innate immune receptors

Liwinski

Zheng

Elinav

2020

Immunological Reviews

View full text Add to dashboard Cite

The discovery of innate immune sensors (pattern recognition receptors, PRRs) has profoundly transformed the notion of innate immunity, in providing a mechanistic basis for host immune interactions with a wealth of environmental signals, leading to a variety of immune‐mediated outcomes including instruction and activation of the adaptive immune arm. As part of this growing understanding of host‐environmental cross talk, an intimate connection has been unveiled between innate immune sensors and signals perceived from the commensal microbiota, which may be regarded as a hub integrating a variety of environmental cues. Among cytosolic PRRs impacting on host homeostasis by interacting with the commensal microbiota are nucleotide‐binding domain, leucine‐rich repeat‐containing protein receptors (NLRs), together with a number of cytosolic DNA sensors and the family of absent in melanoma (AIM)–like receptors (ALRs). NLR sensors have been a particular focus of research, and some NLRs have emerged as key orchestrators of inflammatory responses and host homeostasis. Some NLRs achieve this through the formation of cytoplasmic multiprotein complexes termed inflammasomes. More recently discovered PRRs include retinoic acid‐inducible gene‐I (RIG‐I)–like receptors (RLRs), cyclic GMP‐AMP synthase (cGAS), and STING. In the present review, they summarize recent advancements in knowledge on structure and function of cytosolic PRRs and their roles in host‐microbiota cross talk and immune surveillance. In addition, we discuss their relevance for human health and disease and future therapeutic applications involving modulation of their activation and signaling.

show abstract

“…Upon recognition of mtDNA leaked into the cytoplasm, cGAS synthesizes the second messenger molecule cGAMP, and induces IFN production by STING activation in DENV-infected cells and signals to neighboring cells via gap junctions [ 170 ]. This functional mechanism of mammalian cGAS was also confirmed by infection with intracellular bacteria [ 171 , 172 , 173 , 174 ] and parasites [ 175 , 176 , 177 ] ( Table 2 ). Sensing Mycobacterium tuberculosis ( Mtb ) DNA via the cGAS-STING pathway induces type I IFN and autophagy [ 172 , 173 ], however, these inductions do not contribute to host protection against Mtb infection in mammalian lung cells [ 171 ].…”

Section: Cgasmentioning

confidence: 59%

Cytosolic Sensors for Pathogenic Viral and Bacterial Nucleic Acids in Fish

Mojzesz

Rakus

Chadzińska

et al. 2020

IJMS

View full text Add to dashboard Cite

Recognition of the non-self signature of invading pathogens is a crucial step for the initiation of the innate immune mechanisms of the host. The host response to viral and bacterial infection involves sets of pattern recognition receptors (PRRs), which bind evolutionarily conserved pathogen structures, known as pathogen-associated molecular patterns (PAMPs). Recent advances in the identification of different types of PRRs in teleost fish revealed a number of cytosolic sensors for recognition of viral and bacterial nucleic acids. These are DExD/H-box RNA helicases including a group of well-characterized retinoic acid inducible gene I (RIG-I)-like receptors (RLRs) and non-RLR DExD/H-box RNA helicases (e.g., DDX1, DDX3, DHX9, DDX21, DHX36 and DDX41) both involved in recognition of viral RNAs. Another group of PRRs includes cytosolic DNA sensors (CDSs), such as cGAS and LSm14A involved in recognition of viral and intracellular bacterial dsDNAs. Moreover, dsRNA-sensing protein kinase R (PKR), which has a role in antiviral immune responses in higher vertebrates, has been identified in fish. Additionally, fish possess a novel PKR-like protein kinase containing Z-DNA binding domain, known as PKZ. Here, we review the current knowledge concerning cytosolic sensors for recognition of viral and bacterial nucleic acids in teleosts.

show abstract

Intracellular bacteria engage a STING–TBK1–MVB12b pathway to enable paracrine cGAS–STING signalling

Cited by 108 publications

References 54 publications

Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response

Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response

The microbiome and cytosolic innate immune receptors

Cytosolic Sensors for Pathogenic Viral and Bacterial Nucleic Acids in Fish

Contact Info

Product

Resources

About