The inflammasome: in memory of Dr. Jurg Tschopp

Our plain-English summary of The inflammasome: in memory of Dr. Jurg Tschopp, by M. Dagenais, A. Skeldon, M. Saleh (Cell Death and Differentiation, 2012).

The study

• Authors: M. Dagenais, A. Skeldon, M. Saleh
• Journal: Cell Death and Differentiation
• Published: 2012;19(1):5-12
• Type of article: Historical article
• Cited by: 73 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

A decade ago, Jurg Tschopp introduced the concept of the inflammasome. This exciting discovery of a macromolecular complex that senses 'danger' and initiates the inflammatory response contributed to a renaissance in the fields of innate immunity and cell death. Jurg led the biochemical characterization of the inflammasome complex and demonstrated that spontaneous hyperactivation of this interleukin (IL)-1β processing machinery is the molecular basis of a spectrum of hereditary periodic fever syndromes, caused by mutated forms of the inflammasome scaffolding receptor, NLRP3. The identification of the underlying mechanism in these disorders has led to their now successful therapy, with the use of the IL-1 receptor antagonist in the clinic. Jurg's pioneering work has subsequently defined a number of inflammasome agonists ranging from microbial molecules expressed during infection, to triggers of sterile inflammation, most notably gout-associated uric acid crystals, asbestos, silica and nanoparticles. More recently, Jurg introduced the critical new concept of the metabolic inflammasome, which senses metabolic stress and contributes to the onset of the metabolic syndrome associated with obesity and type 2 diabetes. Jurg was an outstanding and skillful biochemist, an elegant and rigorous researcher often far ahead of his peers. He was a truly amiable person, fair, generous and inspiring, and will be most remembered for his infectious enthusiasm. We write this review article on the inflammasome in his honor and dedicate it to his memory.

In plain English

This article was a review, written as a tribute to the biochemist Jurg Tschopp, of published research on the inflammasome. The inflammasome is a protein complex inside immune cells that senses 'danger' and starts inflammation by activating caspase-1 and the signalling molecule IL-1β. The review reported no new data of its own. The authors described work by Tschopp and colleagues linking the inflammasome to cold-associated periodic syndromes, gout and type 2 diabetes. Asbestos appeared in a list of triggers of inflammation without infection. Citing an earlier study by Tschopp and colleagues, the authors reported that treating macrophages (a type of immune cell) with asbestos or silica caused release of IL-1β in an NLRP3-dependent way. The asbestos fiber type was not named. Tschopp's group first proposed that such large crystals caused 'frustrated phagocytosis' and production of reactive oxygen species, and later pointed to mitochondria as the source. Discussing other agents, the authors warned that laboratory inflammasome results must be interpreted with caution and confirmed in physiological contexts. The authors concluded that Tschopp's work started a new field of immunology.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: narrative review written in memory of Jurg Tschopp
• Who was studied: no study population; the authors reviewed published laboratory, animal and clinical research on the inflammasome, much of it by Tschopp and colleagues
• Exposure: asbestos (fiber type not specified) was discussed as one of several sterile triggers of the NLRP3 inflammasome, alongside uric acid crystals, silica and nanoparticles
• Main results:
  • Citing earlier studies, the authors reported that treatment of macrophages with asbestos, silica, alum, amyloid fibers or hemozoin caused release of IL-1β in an NLRP3-dependent fashion
  • Tschopp and colleagues first proposed that these large crystals led to 'frustrated phagocytosis' and reactive oxygen species production by NADPH oxidase, and later implicated mitochondria as the source of reactive oxygen species
  • The review described Tschopp and colleagues' work on the clinical relevance of the inflammasome in cold-associated periodic syndromes, gout and type 2 diabetes
  • In discussing hemozoin and alum, the authors cautioned that inflammasome activation seen in laboratory (in vitro) studies must be interpreted with caution and validated in physiological contexts
• The authors' conclusion: The authors concluded that Tschopp's work on the inflammasome started a new field of immunology

Topics

Medical terms in this study, explained in our Lexicon: Discovery, Inflammation.

Related studies

• Vimentin regulates activation of the NLRP3 inflammasome — G. dos Santos, M.R. Rogel, et al. (2015)
• Nanoparticles activate the NLR pyrin domain containing 3 (Nlrp3) inflammasome and cause pulmonary inflammation through release of IL-1α and IL-1β — A.S. Yazdi, G. Guarda, et al. (2010)
• Orthopedic wear debris mediated inflammatory osteolysis is mediated in part by NALP3 inflammasome activation — L. Burton, D. Paget, et al. (2013)
• PKC/ROS-Mediated NLRP3 Inflammasome Activation Is Attenuated by Leishmania Zinc-Metalloprotease during Infection — M.T. Shio, J.G. Christian, et al. (2015)
• Inflammasome inhibition under physiological and pharmacological conditions — E.A. Caseley, J.A. Poulter, et al. (2020)
• Long, needle-like carbon nanotubes and asbestos activate the NLRP3 inflammasome through a similar mechanism — J. Palomäki, E. Välimäki, et al. (2011)

Browse return to medical research.