Crosstalk between autophagy and inflammatory signalling pathways: balancing defence and homeostasis

Cadwell, Ken

doi:10.1038/nri.2016.100

Cited by 374 publications

(283 citation statements)

References 180 publications

(221 reference statements)

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“…In particular, the autophagy receptor optineurin is phosphorylated by protein kinase TANK binding kinase 1 (TBK1) to promote autophagy of Salmonella [90]. Linking inflammasome to autophagy during Salmonella infection, both processes can be activated by common pathways such as the damage of the Salmonella -containing vacuole by GBPs [22,91]. …”

Section: Pathogens Differentially Interfere With the Inflammasomes Anmentioning

confidence: 99%

Checks and Balances between Autophagy and Inflammasomes during Infection

Seveau

Turner

Gavrilin

et al. 2018

Journal of Molecular Biology

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Autophagy and inflammasome complex assembly are physiological processes that control homeostasis, inflammation, and immunity. Autophagy is a ubiquitous pathway that degrades cytosolic macromolecules or organelles, as well as intracellular pathogens. Inflammasomes are multi-protein complexes that assemble in the cytosol of cells upon detection of pathogen- or danger-associated molecular patterns. A critical outcome of inflammasome assembly is the activation of the serine protease caspase-1, which activates the pro-inflammatory cytokine precursors pro-IL-1β and pro-IL-18. Studies on chronic inflammatory diseases, heart diseases, Alzheimer's disease, and multiple sclerosis revealed that autophagy and inflammasomes intersect and regulate each other. In the context of infectious diseases, however, less is known about the interplay between autophagy and inflammasome assembly, although it is becoming evident that pathogens have evolved multiple strategies to inhibit and/or subvert these pathways and to take advantage of their intricate crosstalk. An improved appreciation of these pathways and their subversion by diverse pathogens is expected to help in the design of anti-infective therapeutic interventions.

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Section: Pathogens Differentially Interfere With the Inflammasomes Anmentioning

confidence: 99%

Checks and Balances between Autophagy and Inflammasomes during Infection

Seveau

Turner

Gavrilin

et al. 2018

Journal of Molecular Biology

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“…autophagy in an attempt to protect the host from excessive inflammation (7). This mutual regulation is important to understand, as it applies to multiple disease processes, and in this review we discuss currently available information about the two-way street of regulation that exists between inflammasomes and autophagy.…”

mentioning

confidence: 99%

Inflammasome and Autophagy Regulation: A Two-way Street

Sun

Fan

Billiar

et al. 2017

Mol Med

165

133

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Inflammation plays a significant role in protecting hosts against pathogens. Inflammation induced by noninfectious endogenous agents can be detrimental and, if excessive, can result in organ and tissue damage. The inflammasome is a major innate immune pathway that can be activated via both exogenous pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs). Inflammasome activation involves formation and oligomerization of a protein complex including a nucleotide oligomerization domain (NOD)-like receptor (NLR), an adaptor protein and pro-caspase-1. This then allows cleavage and activation of caspase-1, followed by downstream cleavage and release of proinflammatory cytokines interleukin (IL)-1β and IL-18 from innate immune cells. Hyperinflammation caused by unrestrained inflammasome activation is linked with multiple inflammatory diseases, including inflammatory bowel disease, Alzheimer's disease and multiple sclerosis. So there is an understandable rush to understand mechanisms that regulate such potent inflammatory pathways. Autophagy has now been identified as a main regulator of inflammasomes. Autophagy is a vital intracellular process involved in cellular homeostasis, recycling and removal of damaged organelles (eg, mitochondria) and intracellular pathogens. Autophagy is regulated by proteins that are important in endosomal/phagosomal pathways, as well as by specific autophagy proteins coded for by autophagy-related genes. Cytosolic components are surrounded and contained by a double-membraned vesicle, which then fuses with lysosomes to enable degradation of the contents. Autophagic removal of intracellular DAMPs, inflammasome components or cytokines can reduce inflammasome activation. Similarly, inflammasomes can regulate the autophagic process, allowing for a two-way mutual regulation of inflammation that may hold the key for treatment of multiple diseases.

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“…The autophagic pathway utilizes a well‐orchestrated cascade of forming and targeting autophagosomes carried out by autophagy‐related proteins (ATGs) (Levy et al., 2017). Under physiological conditions, the autophagic cascade is initiated following the activation of AMPK by energy deprivation, which consequently exerts inhibitory effects on mTORC1 (mTOR complex 1) (Cadwell, 2016; Cheng, Zhang, Ji, Tao, & Guo, 2016). Next, the activity of the transcription factor EB (TFEB) is enhanced as a result of mTORC1 inhibition, facilitating the transcriptional induction of autophagy‐relevant genes, including Atg5, Atg12, and Atg16 (Noda, 2017).…”

Section: Pathological Association Between Autophagic Pathways and Alzmentioning

confidence: 99%

The emerging roles of protein homeostasis‐governing pathways in Alzheimer's disease

et al. 2018

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Pathways governing protein homeostasis are involved in maintaining the structural, quantitative, and functional stability of intracellular proteins and involve the ubiquitin–proteasome system, autophagy, endoplasmic reticulum, and mTOR pathway. Due to the broad physiological implications of protein homeostasis pathways, dysregulation of proteostasis is often involved in the development of multiple pathological conditions, including Alzheimer's disease (AD). Similar to other neurodegenerative diseases that feature pathogenic accumulation of misfolded proteins, Alzheimer's disease is characterized by two pathological hallmarks, amyloid‐β (Aβ) plaques and tau aggregates. Knockout or transgenic overexpression of various proteostatic components in mice results in AD‐like phenotypes. While both Aβ plaques and tau aggregates could in turn enhance the dysfunction of these proteostatic pathways, eventually leading to apoptotic or necrotic neuronal death and pathogenesis of Alzheimer's disease. Therefore, targeting the components of proteostasis pathways may be a promising therapeutic strategy against Alzheimer's disease.

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Crosstalk between autophagy and inflammatory signalling pathways: balancing defence and homeostasis

Cited by 374 publications

References 180 publications

Checks and Balances between Autophagy and Inflammasomes during Infection

Checks and Balances between Autophagy and Inflammasomes during Infection

Inflammasome and Autophagy Regulation: A Two-way Street

The emerging roles of protein homeostasis‐governing pathways in Alzheimer's disease

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