Inflammasomes as Targets for Adjuvants

Ivanov, Konstantin; Garanina, Ekaterina; Rizvanov, Albert A.; Khaiboullina, Svetlana

doi:10.3390/pathogens9040252

Cited by 27 publications

(23 citation statements)

References 129 publications

(145 reference statements)

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“…Experiments utilizing analogs of dsRNA (poly-I:C) and ssRNA (ssRNA40) demonstrated that an NLRP3mediated response could be activated by 'virus mimetic' RNA species (Allen et al 2009). Whereas the NLRP3 inflammasome is an essential component in host defense against infection through sensing of viral RNA (Ivanov et al 2020), its overshooting activity can be highly destructive. An excessive inflammatory response results in the progression of ARDS, with the NLRP3 inflammasome as key player.…”

Section: Introductionmentioning

confidence: 99%

Erythropoietin as candidate for supportive treatment of severe COVID-19

Ehrenreich

Weißenborn

Begemann

et al. 2020

Mol Med

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In light of the present therapeutic situation in COVID-19, any measure to improve course and outcome of seriously affected individuals is of utmost importance. We recap here evidence that supports the use of human recombinant erythropoietin (EPO) for ameliorating course and outcome of seriously ill COVID-19 patients. This brief expert review grounds on available subject-relevant literature searched until May 14, 2020, including Medline, Google Scholar, and preprint servers. We delineate in brief sections, each introduced by a summary of respective COVID-19 references, how EPO may target a number of the gravest sequelae of these patients. EPO is expected to: (1) improve respiration at several levels including lung, brainstem, spinal cord and respiratory muscles; (2) counteract overshooting inflammation caused by cytokine storm/ inflammasome; (3) act neuroprotective and neuroregenerative in brain and peripheral nervous system. Based on this accumulating experimental and clinical evidence, we finally provide the research design for a double-blind placebo-controlled randomized clinical trial including severely affected patients, which is planned to start shortly.

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Section: Introductionmentioning

confidence: 99%

Erythropoietin as candidate for supportive treatment of severe COVID-19

Ehrenreich

Weißenborn

Begemann

et al. 2020

Mol Med

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“…Inflammasomes are an essential part of the innate immune system and their activation can stimulate the adaptive immune system; thus, they are often the targets for vaccine adjuvants [ 84 ]. The role of QS-21 in activating NOD-like receptor protein 3 (NLRP3) inflammasome seems to be complicated.…”

Section: Mechanism Studies Of Qs-21mentioning

confidence: 99%

Natural and Synthetic Saponins as Vaccine Adjuvants

Wang

2021

Vaccines

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Saponin adjuvants have been extensively studied for their use in veterinary and human vaccines. Among them, QS-21 stands out owing to its unique profile of immunostimulating activity, inducing a balanced Th1/Th2 immunity, which is valuable to a broad scope of applications in combating various microbial pathogens, cancers, and other diseases. It has recently been approved for use in human vaccines as a key component of combination adjuvants, e.g., AS01b in Shingrix® for herpes zoster. Despite its usefulness in research and clinic, the cellular and molecular mechanisms of QS-21 and other saponin adjuvants are poorly understood. Extensive efforts have been devoted to studies for understanding the mechanisms of QS-21 in different formulations and in different combinations with other adjuvants, and to medicinal chemistry studies for gaining mechanistic insights and development of practical alternatives to QS-21 that can circumvent its inherent drawbacks. In this review, we briefly summarize the current understandings of the mechanism underlying QS-21’s adjuvanticity and the encouraging results from recent structure-activity-relationship (SAR) studies.

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“…As a whole, the ability of ASC specks to aggregate cytosolic proteins, to be released into the extracellular space, to localize in subcapsular niche of lymph nodes and to have controlled degradation when phagocytized gives specks the potential to contribute to antigen presentation during an infection or even in vaccination. Moreover, alum adjuvants used in human vaccines have their activity linked to the activation of ASC specks producing NLRP3 inflammasome [29][30][31].…”

Section: Physiological Roles Of Easc Asc Specks In Adaptive Immune Responsementioning

confidence: 99%

“…Thus, ASC specks present important roles in adaptive immunity independently of inflammasome activation, related to antigen uptake and presentation and polarization of immune response [31,33].…”

Section: Physiological Roles Of Easc Asc Specks In Adaptive Immune Responsementioning

confidence: 99%

Unknown/enigmatic functions of extracellular ASC

2021

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Apoptosis-associated speck-like protein containing a caspase recruit domain (ASC), encoded by PYCARD gene, is a 22 kDa small molecule, which aggregates into ASC specks during inflammasome activation. ASC protein is an adaptor protein present in several inflammasome complexes that performs several intra-and extracellular functions, in monomeric form or as ASC specks, during physiological and pathological processes related to inflammation and adaptive immunity. Extracellular ASC specks (eASC specks) released during cell death by pyroptosis can contribute as a danger signal to the propagation of inflammation via phagocytosis and activation of surrounding cells. ASC specks are found in the circulation of patients with chronic inflammatory diseases and have been considered as relevant blood biomarkers of inflammation. eASC amplifies the inflammatory signal, may induce the production of autoantibodies, transports molecules that bind to this complex, contributing to the generation of antibodies, and can induce the maturation of cytokines promoting the modelling of the adaptive immunity. Although several advances have been registered in the last 21 years, there are numerous unknown or enigmatic gaps in the understanding of the role of eASC specks in the organism. Here, we provide an overview about the ASC protein focusing on the probable roles of eASC specks in several diseases, up to the most recent studies concerning COVID-19.

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Inflammasomes as Targets for Adjuvants

Cited by 27 publications

References 129 publications

Erythropoietin as candidate for supportive treatment of severe COVID-19

Erythropoietin as candidate for supportive treatment of severe COVID-19

Natural and Synthetic Saponins as Vaccine Adjuvants

Unknown/enigmatic functions of extracellular ASC

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