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Review
. 2010 Feb 26;6(2):e1000661.
doi: 10.1371/journal.ppat.1000661.

IL-1beta processing in host defense: beyond the inflammasomes

Mihai G Netea  1 , Anna Simon, Frank van de Veerdonk, Bart-Jan Kullberg, Jos W M Van der Meer, Leo A B Joosten
Affiliations
Review

IL-1beta processing in host defense: beyond the inflammasomes

Mihai G Netea et al. PLoS Pathog. .

Abstract

Stimulation and release of proinflammatory cytokines is an essential step for the activation of an effective innate host defense, and subsequently for the modulation of adaptive immune responses. Interleukin-1beta (IL-1beta) and IL-18 are important proinflammatory cytokines that on the one hand activate monocytes, macropages, and neutrophils, and on the other hand induce Th1 and Th17 adaptive cellular responses. They are secreted as inactive precursors, and the processing of pro-IL-1beta and pro-IL-18 depends on cleavage by proteases. One of the most important of these enzymes is caspase-1, which in turn is activated by several protein platforms called the inflammasomes. Inflammasome activation differs in various cell types, and knock-out mice defective in either caspase-1 or inflammasome components have an increased susceptibility to several types of infections. However, in other infections and in models of sterile inflammation, caspase-1 seems to be less important, and alternative mechanisms such as neutrophil-derived serine proteases or proteases released from microbial pathogens can process and activate IL-1beta. In conclusion, IL-1beta/IL-18 processing during infection is a complex process in which the inflammasomes are only one of several activation mechanisms.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. The prototypical NLRP3 and NLRC4 inflammasomes.
(A) The NLRP3 inflammasome is activated by both bacterial (e.g., MDP, bacterial RNA, β-glucan), exogenous (e.g., silica, alum), and endogenous (e.g., uric acid cristals, ATP) stimuli. (B) The NLRC4 inflammasome is activated by flagellin in a TLR5-independent fashion.
Figure 2
Figure 2. Diagram representing the differential caspase-1/IL-1β activation pathways in monocytes and macrophages.
Caspase-1 is constitutively activated in monocytes, and these cells release mature IL-1β after single stimulation with TLR ligands. IL-1β secretion is induced by endogenously-released ATP. In contrast, macrophages need a double stimulation: one stimulus (TLR-ligands) induces transcription, and a second stimulus (ATP) induces IL-1β secretion.
Figure 3
Figure 3. Inflammasome-independent processing of pro-IL-1β.
In addition to caspase-1-dependent activation, pro-IL-1β can also be processed by neutrophil-derived serine proteases, or pathogen-derived proteases.
See this image and copyright information in PMC

References

    1. Marodi L, Korchak HM, Johnston RB., Jr Mechanisms of host defense against Candida species. 1. Phagocytosis by monocytes and monocyte-derived macrophages. J Immunol. 1991;146:2783–2789. - PubMed
    1. Taylor PR, Martinez-Pomares L, Stacey M, Lin HH, Brown GD, et al. Macrophage receptors and immune recognition. Annu Rev Immunol. 2005;23:901–944. - PubMed
    1. Orange JS, Ballas ZK. Natural killer cells in human health and disease. Clin Immunol. 2006;118:1–10. - PubMed
    1. Lin J, Ziring D, Desai S, Kim S, Wong M, et al. TNFalpha blockade in human diseases: an overview of efficacy and safety. Clin Immunol. 2008;126:13–30. - PMC - PubMed
    1. Ottenhoff TH, Verreck FA, Lichtenauer-Kaligis EG, Hoeve MA, Sanal O, et al. Genetics, cytokines and human infectious disease: lessons from weakly pathogenic mycobacteria and salmonellae. Nat Genet. 2002;32:97–105. - PubMed

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