Dectin-1 is an extracellular pathogen sensor for the induction and processing of IL-1β via a noncanonical caspase-8 inflammasome

Gringhuis, Sonja I.; Kaptein, Tanja M.; Wevers, Brigitte A.; Theelen, Bart; Vlist, Michiel van der; Boekhout, Teun; Geijtenbeek, Teunis B. H.

doi:10.1038/ni.2222

Cited by 542 publications

(443 citation statements)

References 48 publications

Supporting

Mentioning

408

Contrasting

Unclassified

Order By: Relevance

“…Dectin-1-mediated signaling also stimulates the formation of the caspase-8-MALT1-ASC complex, and then the activated caspase-8 produces mature IL-1b (Fig. 5) (Gringhuis et al 2012). The dectin-1 pathway is also known for its ability to activate the canonical caspase-1 inflammasome (Hise et al 2009).…”

Section: Caspase-8mentioning

confidence: 99%

“…Furthermore, in response to pathogen infection, caspase-8 is involved in the processing of pro-IL-1b/ IL-18 to yield active cytokines in an inflammasome-independent manner (Latz et al 2013). In contrast to caspase-1, caspase-8 is activated by dectin-1, TLRs, and Fas located on the plasma membrane (Gringhuis et al 2012;Lemmers et al 2007;Strasser et al 2009). Recently, Fas-activated caspase-8 has been shown to contribute to the production of inflammatory cytokines and the host defense towards pathogenic bacterial infections (Uchiyama et al 2013).…”

Section: Differentiationmentioning

confidence: 99%

See 1 more Smart Citation

Caspases as the Key Effectors of Inflammatory Responses Against Bacterial Infection

Uchiyama

Tsutsui

2014

Arch. Immunol. Ther. Exp.

View full text Add to dashboard Cite

show abstract

Section: Caspase-8mentioning

confidence: 99%

Section: Differentiationmentioning

confidence: 99%

Caspases as the Key Effectors of Inflammatory Responses Against Bacterial Infection

Uchiyama

Tsutsui

2014

Arch. Immunol. Ther. Exp.

View full text Add to dashboard Cite

show abstract

“…An interesting candidate is the caspase-8 inflammasome triggered in response to dectin-1 signaling. 28 It would be interesting to evaluate the role of this system since dectin-1 is a classical receptor in immune response to fungi.…”

Section: Discussionmentioning

confidence: 99%

IL-1 signaling inhibits Trichophyton rubrum conidia development and modulates the IL-17 response in vivo

2015

View full text Add to dashboard Cite

Dermatophytosis are one of the most common fungal infections in the world. They compromise keratinized tissues and the main etiological agent is Trichophyton rubrum. Macrophages are key cells in innate immunity and prominent sources of IL-1b, a potent inflammatory cytokine whose main production pathway is by the activation of inflammasomes and caspase-1. However, the role of inflammasomes and IL-1 signaling against T.rubrum has not been reported. In this work, we observed that bone marrow-derived macrophages produce IL-1b in response to T.rubrum conidia in a NLRP3-, ASC-and caspase-1-dependent fashion. Curiously, lack of IL-1 signaling promoted hyphae development, uncovering a protective role for IL-1b in macrophages. In addition, mice lacking IL-1R showed reduced IL-17 production, a key cytokine in the antifungal defense, in response to T.rubrum. Our findings point to a prominent role of IL-1 signaling in the immune response to T.rubrum, opening the venue for the study of this pathway in other fungal infections.

show abstract

“…11 Caspase-8 is also activated downstream of the NLRP3, AIM2 and NLRC4 inflammasomes in response to canonical triggers in macrophages 4,[12][13][14] or downstream of Dectin-1 in dendritic cells. [15][16][17] The activation of caspase-8 in leukocytes requires ASC and regulates the non-canonical maturation of IL-1β. However in caspase-1/11-deficient macrophages, caspase-8 also regulates apoptosis downstream of AIM2 and NLRP3 inflammasomes.…”

mentioning

confidence: 99%

NLRP3 regulates a non-canonical platform for caspase-8 activation during epithelial cell apoptosis

et al. 2016

View full text Add to dashboard Cite

Nod-like receptor, pyrin containing 3 (NLRP3) is characterized primarily as a canonical caspase-1 activating inflammasome in macrophages. NLRP3 is also expressed in the epithelium of the kidney and gut; however, its function remains largely undefined. Primary mouse tubular epithelial cells (TEC) lacking Nlrp3 displayed reduced apoptosis downstream of the tumor necrosis factor (TNF) receptor and CD95. TECs were identified as type II apoptotic cells that activated caspase-8, tBid and mitochondrial apoptosis via caspase-9, responses that were reduced in Nlrp3 − / − cells. The activation of caspase-8 during extrinsic apoptosis induced by TNFα/cycloheximide (TNFα/CHX) was dependent on adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) and completely independent of caspase-1 or caspase-11. TECs and primary human proximal tubular epithelial cells (HPTC) did not activate a canonical inflammasome, caspase-1, or IL-1β secretion in response to TNFα/CHX or NLRP3-dependent triggers, such as ATP or nigericin. In cell fractionation studies and by confocal microscopy, NLRP3 colocalized with ASC and caspase-8 in speck-like complexes at the mitochondria during apoptosis. The formation of NLRP3/ASC/caspase-8 specks in response to TNFα/ CHX was downstream of TNFR signaling and dependent on potassium efflux. Epithelial ASC specks were present in enteroids undergoing apoptosis and in the injured tubules of wild-type but not Nlrp3 − / − or ASC − / − mice following ureteric unilateral obstruction in vivo. These data show that NLRP3 and ASC form a conserved non-canonical platform for caspase-8 activation, independent of the inflammasome that regulates apoptosis within epithelial cells.

show abstract

Dectin-1 is an extracellular pathogen sensor for the induction and processing of IL-1β via a noncanonical caspase-8 inflammasome

Cited by 542 publications

References 48 publications

Caspases as the Key Effectors of Inflammatory Responses Against Bacterial Infection

Caspases as the Key Effectors of Inflammatory Responses Against Bacterial Infection

IL-1 signaling inhibits Trichophyton rubrum conidia development and modulates the IL-17 response in vivo

NLRP3 regulates a non-canonical platform for caspase-8 activation during epithelial cell apoptosis

Contact Info

Product

Resources

About