IL-1 family cytokines serve as 'activity recognition receptors' for aberrant protease activity indicative of danger

Martin, Séamus J.; Frezza, Valentina; Davidovich, P. B.; Najda, Zaneta; Clancy, Danielle M.

doi:10.1016/j.cyto.2022.155935

Cited by 10 publications

(17 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been suggested that protease activity may serve as a proxy for the detection of helminth worms by the immune system (4)(5)(6), and that the protease activity associated with common allergens may be the reason that such agents trigger paradoxically strong inflammatory responses despite their harmless nature. Thus, in addition to the detection of conserved 'non-self' molecular patterns, the immune system may have co-evolved a system to detect aberrant molecular activities that have the potential to perturb normal tissue and cellular homeostasis, as a proxy for the detection of pathogen activity or tissue necrosis (11). This concept is well established in plants, where numerous NLR proteins are involved in sensing diverse enzymatic activities (including proteolytic activity) associated with pathogens, in a process that has been termed 'effector-triggered immunity' (reviewed in (34,35)).…”

Section: Discussionmentioning

confidence: 99%

“…Emerging evidence suggests that the proteolytic activities associated with common environmental allergens, as well as helminth worms, play a key role in triggering inflammation (7,8), either by directly acting on Basophils or Mast cells to promote IL-4 release (5,6), or through proteolytic processing and activating the Th2-polarizing IL-1 family cytokine, IL-33 (9,10). Thus, in addition to the detection of PAMPs and DAMPs, emerging evidence suggests that inflammation may also be initiated via molecules that are capable of sensing aberrant enzymatic activities-such as protease activity-in tissue or cellular compartments where these activities are normally not present (reviewed in Martin et al (11). Such 'activity recognition receptors' (ARRs) may complement PRRs as instigators of inflammation through detecting molecular activities, rather than molecular patterns, associated with non-self entities (11).…”

Section: Introductionmentioning

confidence: 99%

“…Pathogens and other non-self entities that infiltrate barrier surfaces harbor proteases, as well as other enzymes, that may serve as potent instigators of inflammation through activating ARRs, either directly, or through processing ARR ligands, such as members of the extended IL-1 family (11). IL-1 family cytokines are pleiotropic cytokines released during infection or injury and play key roles as initiators of inflammation (3,(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

“…Thus, in addition to the detection of PAMPs and DAMPs, emerging evidence suggests that inflammation may also be initiated via molecules that are capable of sensing aberrant enzymatic activities—such as protease activity—in tissue or cellular compartments where these activities are normally not present (reviewed in Martin et al. ( 11 ). Such ‘activity recognition receptors’ (ARRs) may complement PRRs as instigators of inflammation through detecting molecular activities , rather than molecular patterns , associated with non-self entities ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

“…( 11 ). Such ‘activity recognition receptors’ (ARRs) may complement PRRs as instigators of inflammation through detecting molecular activities , rather than molecular patterns , associated with non-self entities ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

IL-1α and IL-36 Family Cytokines Can Undergo Processing and Activation by Diverse Allergen-Associated Proteases

et al. 2022

Self Cite

View full text Add to dashboard Cite

Inflammation driven by environmental allergens is an important source of morbidity in diseases such as asthma and eczema. How common allergens promote inflammation is still poorly understood, but previous studies have implicated the protease activity associated with many allergens as an important component of the pro-inflammatory properties of these agents. The IL-1 family cytokine, IL-33, has recently been shown to undergo processing and activation by proteases associated with multiple common allergens. However, it remains unclear whether the sensing of exogenous protease activity—as a proxy for the detection of invasive microbes, allergens and parasitic worms—is a general property of IL-1 family cytokines. In common with the majority of IL-1 family members, cytokines within the IL-36 sub-family (IL-36α, IL-36β and IL-36γ) are expressed as inactive precursors that require proteolysis within their N-termini for activation. Here we show that proteases associated with multiple common allergens of plant, insect, fungal and bacterial origin (including: Aspergillus fumigatus, ragweed, rye, house dust mite, cockroach and Bacillus licheniformis) are capable of processing and activating IL-36 family cytokines, with IL-36β being particularly susceptible to activation by multiple allergens. Furthermore, extracts from several allergens also processed and enhanced IL-1α activity. This suggests that multiple IL-1 family cytokines may serve as sentinels for exogenous proteases, coupling detection of such activity to unleashing the pro-inflammatory activity of these cytokines. Taken together with previous data on the diversity of proteases capable of activating IL-1 family cytokines, this suggests that members of this cytokine family may function as ‘activity recognition receptors’ for aberrant protease activity associated with infection, tissue injury or programmed necrosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

IL-1α and IL-36 Family Cytokines Can Undergo Processing and Activation by Diverse Allergen-Associated Proteases

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

Discriminating Between Apoptosis, Necrosis, Necroptosis, and Ferroptosis by Microscopy and Flow Cytometry

Costigan,

Hollville,

Martin

2023

Current Protocols

Self Cite

View full text Add to dashboard Cite

Apoptosis is a mode of programmed cell death that plays important roles in tissue sculpting during development, in the maintenance of tissue homeostasis in the adult, and in the eradication of injured or infected cells during pathological processes. Numerous physiological as well as pathological stimuli trigger apoptosis, such as engagement of plasma‐membrane‐associated Fas, TRAIL, or TNF receptors, growth factor deprivation, hypoxia, radiation, and exposure to diverse cytotoxic drugs. Apoptosis is coordinated by members of the caspase family of cysteine proteases, which, upon activation, trigger a series of dramatic morphological and biochemical changes including retraction from the substratum, cell shrinkage, extensive and protracted plasma membrane blebbing, chromatin condensation, DNA hydrolysis, nuclear fragmentation, and proteolytic cleavage of numerous caspase substrates. These dramatic structural and biochemical alterations result not only in the controlled dismantling of the cell, but also in the rapid recognition and removal of apoptotic cells by phagocytes through the cell surface display of phagocytotic triggers such as phosphatidylserine. Necrosis, which is typically nonprogrammed or imposed upon the cell by overwhelming membrane or organelle damage, is characterized by high‐amplitude cell swelling, followed by rapid plasma membrane rupture and release of cellular contents into the extracellular space. Necrosis is often provoked by infectious agents or severe departure from physiological conditions due to toxins, temperature extremes, or physical injury. However, forms of programmed necrosis (necroptosis, pyroptosis, ferroptosis) can also occur in specific circumstances. Nonprogrammed and programmed necrosis can be distinguished from apoptosis by morphological features, based on the rapid uptake of vital dyes, and through the application of specific inhibitors of key molecules associated with the latter modes of cell death. This unit describes protocols for the measurement of apoptosis and necrosis and for distinguishing apoptosis from programmed as well as conventional necrosis. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.Basic Protocol 1: Analysis of cell morphology by phase‐contrast microscopyAlternative Protocol 1: Assessment of morphological changes using eosin‐methylene blue stainingAlternative Protocol 2: Analysis of nuclear morphology by fluorescence microscopySupport Protocol: Preparation of cytospinsBasic Protocol 2: Measurement of plasma membrane composition with annexin V and propidium iodideBasic Protocol 3: Measurement of DNA fragmentation by flow cytometryAlternative Protocol 3: Analysis of DNA fragmentation by the TUNEL assayBasic Protocol 4: Measurement of caspase activation by flow cytometryBasic Protocol 5: Discriminating between apoptosis, necrosis, necroptosis, and ferroptosis

show abstract

Special Issue “IL-1 family cytokines in host defense, inflammation and cancer”

Palmer

Gabay

2022

Cytokine

View full text Add to dashboard Cite

IL-1 family cytokines serve as 'activity recognition receptors' for aberrant protease activity indicative of danger

Cited by 10 publications

References 87 publications

IL-1α and IL-36 Family Cytokines Can Undergo Processing and Activation by Diverse Allergen-Associated Proteases

IL-1α and IL-36 Family Cytokines Can Undergo Processing and Activation by Diverse Allergen-Associated Proteases

Discriminating Between Apoptosis, Necrosis, Necroptosis, and Ferroptosis by Microscopy and Flow Cytometry

Special Issue “IL-1 family cytokines in host defense, inflammation and cancer”

Contact Info

Product

Resources

About