Bypassing pathogen-induced inflammasome activation for the regulation of interleukin-1β production by the fungal pathogen Candida albicans

Frank L van de Veerdonk, Leo A B Joosten, Isabel Devesa, Hector M Mora-Montes, Thirumala-Devi Kanneganti, Charles A Dinarello, Jos W M Van Der Meer, Neil A R Gow, Bart Jan Kullberg, Mihai G Netea

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Interleukin (IL)-1beta has an important role in antifungal defense mechanisms. The inflammasome is thought to be required for caspase-1 activation and processing of the inactive precursor pro-IL-1beta. The aim of the present study was to investigate the pathways of IL-1beta production induced by Candida albicans in human monocytes. METHODS: Human mononuclear cells were stimulated with C. albicans or mutant strains defective in mannosylation or chitin. Receptors were blocked with specific antagonists, and the IL-1beta concentration was measured. RESULTS: Human primary monocytes produce bioactive IL-1beta when stimulated with C. albicans. The transcription of IL-1beta was induced through mannose receptor (MR), Toll-like receptor (TLR) 2, and dectin-1 but not through TLR4 and TLR9. N-mannan-linked residues, chitin, and beta-glucan from C. albicans are important for IL-1beta stimulation. Surprisingly, processing and secretion of IL-1beta in monocytes did not require pathogen-mediated inflammasome activation, because of the constitutive activation of caspase-1 and the capability of monocytes to release endogenous adenosine-5'-triphosphate. CONCLUSIONS: This study is the first dissection of the molecular mechanisms of IL-1beta production by a fungal pathogen. Transcription through mannan/chitin/MR and beta-glucan/dectin-1/TLR2 induces production of IL-1beta by C. albicans in human monocytes, whereas processing of IL-1beta is mediated by constitutively active caspase-1.
Original languageEnglish
Pages (from-to)1087-1096
Number of pages10
JournalThe journal of infectious diseases
Volume199
Issue number7
DOIs
Publication statusPublished - 1 Apr 2009

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Inflammasomes
Candida albicans
Interleukin-1beta
Interleukin-1
Monocytes
Caspase 1
Chitin
Mannans
beta-Glucans
Toll-Like Receptor 2
Dissection
Adenosine Triphosphate

Keywords

  • animals
  • apoptosis regulatory proteins
  • calcium-binding proteins
  • Candida albicans
  • carrier proteins
  • caspase 1
  • cells, cultured
  • humans
  • inflammation
  • interleukin-1beta
  • leukocytes, mononuclear
  • macrophages
  • mice

Cite this

van de Veerdonk, F. L., Joosten, L. A. B., Devesa, I., Mora-Montes, H. M., Kanneganti, T-D., Dinarello, C. A., ... Netea, M. G. (2009). Bypassing pathogen-induced inflammasome activation for the regulation of interleukin-1β production by the fungal pathogen Candida albicans. The journal of infectious diseases, 199(7), 1087-1096. https://doi.org/10.1086/597274

Bypassing pathogen-induced inflammasome activation for the regulation of interleukin-1β production by the fungal pathogen Candida albicans. / van de Veerdonk, Frank L; Joosten, Leo A B; Devesa, Isabel; Mora-Montes, Hector M; Kanneganti, Thirumala-Devi; Dinarello, Charles A; Van Der Meer, Jos W M; Gow, Neil A R; Kullberg, Bart Jan; Netea, Mihai G.

In: The journal of infectious diseases, Vol. 199, No. 7, 01.04.2009, p. 1087-1096.

Research output: Contribution to journalArticle

van de Veerdonk, FL, Joosten, LAB, Devesa, I, Mora-Montes, HM, Kanneganti, T-D, Dinarello, CA, Van Der Meer, JWM, Gow, NAR, Kullberg, BJ & Netea, MG 2009, 'Bypassing pathogen-induced inflammasome activation for the regulation of interleukin-1β production by the fungal pathogen Candida albicans', The journal of infectious diseases, vol. 199, no. 7, pp. 1087-1096. https://doi.org/10.1086/597274
van de Veerdonk, Frank L ; Joosten, Leo A B ; Devesa, Isabel ; Mora-Montes, Hector M ; Kanneganti, Thirumala-Devi ; Dinarello, Charles A ; Van Der Meer, Jos W M ; Gow, Neil A R ; Kullberg, Bart Jan ; Netea, Mihai G. / Bypassing pathogen-induced inflammasome activation for the regulation of interleukin-1β production by the fungal pathogen Candida albicans. In: The journal of infectious diseases. 2009 ; Vol. 199, No. 7. pp. 1087-1096.
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title = "Bypassing pathogen-induced inflammasome activation for the regulation of interleukin-1β production by the fungal pathogen Candida albicans",
abstract = "BACKGROUND: Interleukin (IL)-1beta has an important role in antifungal defense mechanisms. The inflammasome is thought to be required for caspase-1 activation and processing of the inactive precursor pro-IL-1beta. The aim of the present study was to investigate the pathways of IL-1beta production induced by Candida albicans in human monocytes. METHODS: Human mononuclear cells were stimulated with C. albicans or mutant strains defective in mannosylation or chitin. Receptors were blocked with specific antagonists, and the IL-1beta concentration was measured. RESULTS: Human primary monocytes produce bioactive IL-1beta when stimulated with C. albicans. The transcription of IL-1beta was induced through mannose receptor (MR), Toll-like receptor (TLR) 2, and dectin-1 but not through TLR4 and TLR9. N-mannan-linked residues, chitin, and beta-glucan from C. albicans are important for IL-1beta stimulation. Surprisingly, processing and secretion of IL-1beta in monocytes did not require pathogen-mediated inflammasome activation, because of the constitutive activation of caspase-1 and the capability of monocytes to release endogenous adenosine-5'-triphosphate. CONCLUSIONS: This study is the first dissection of the molecular mechanisms of IL-1beta production by a fungal pathogen. Transcription through mannan/chitin/MR and beta-glucan/dectin-1/TLR2 induces production of IL-1beta by C. albicans in human monocytes, whereas processing of IL-1beta is mediated by constitutively active caspase-1.",
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AU - van de Veerdonk, Frank L

AU - Joosten, Leo A B

AU - Devesa, Isabel

AU - Mora-Montes, Hector M

AU - Kanneganti, Thirumala-Devi

AU - Dinarello, Charles A

AU - Van Der Meer, Jos W M

AU - Gow, Neil A R

AU - Kullberg, Bart Jan

AU - Netea, Mihai G

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N2 - BACKGROUND: Interleukin (IL)-1beta has an important role in antifungal defense mechanisms. The inflammasome is thought to be required for caspase-1 activation and processing of the inactive precursor pro-IL-1beta. The aim of the present study was to investigate the pathways of IL-1beta production induced by Candida albicans in human monocytes. METHODS: Human mononuclear cells were stimulated with C. albicans or mutant strains defective in mannosylation or chitin. Receptors were blocked with specific antagonists, and the IL-1beta concentration was measured. RESULTS: Human primary monocytes produce bioactive IL-1beta when stimulated with C. albicans. The transcription of IL-1beta was induced through mannose receptor (MR), Toll-like receptor (TLR) 2, and dectin-1 but not through TLR4 and TLR9. N-mannan-linked residues, chitin, and beta-glucan from C. albicans are important for IL-1beta stimulation. Surprisingly, processing and secretion of IL-1beta in monocytes did not require pathogen-mediated inflammasome activation, because of the constitutive activation of caspase-1 and the capability of monocytes to release endogenous adenosine-5'-triphosphate. CONCLUSIONS: This study is the first dissection of the molecular mechanisms of IL-1beta production by a fungal pathogen. Transcription through mannan/chitin/MR and beta-glucan/dectin-1/TLR2 induces production of IL-1beta by C. albicans in human monocytes, whereas processing of IL-1beta is mediated by constitutively active caspase-1.

AB - BACKGROUND: Interleukin (IL)-1beta has an important role in antifungal defense mechanisms. The inflammasome is thought to be required for caspase-1 activation and processing of the inactive precursor pro-IL-1beta. The aim of the present study was to investigate the pathways of IL-1beta production induced by Candida albicans in human monocytes. METHODS: Human mononuclear cells were stimulated with C. albicans or mutant strains defective in mannosylation or chitin. Receptors were blocked with specific antagonists, and the IL-1beta concentration was measured. RESULTS: Human primary monocytes produce bioactive IL-1beta when stimulated with C. albicans. The transcription of IL-1beta was induced through mannose receptor (MR), Toll-like receptor (TLR) 2, and dectin-1 but not through TLR4 and TLR9. N-mannan-linked residues, chitin, and beta-glucan from C. albicans are important for IL-1beta stimulation. Surprisingly, processing and secretion of IL-1beta in monocytes did not require pathogen-mediated inflammasome activation, because of the constitutive activation of caspase-1 and the capability of monocytes to release endogenous adenosine-5'-triphosphate. CONCLUSIONS: This study is the first dissection of the molecular mechanisms of IL-1beta production by a fungal pathogen. Transcription through mannan/chitin/MR and beta-glucan/dectin-1/TLR2 induces production of IL-1beta by C. albicans in human monocytes, whereas processing of IL-1beta is mediated by constitutively active caspase-1.

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KW - apoptosis regulatory proteins

KW - calcium-binding proteins

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KW - carrier proteins

KW - caspase 1

KW - cells, cultured

KW - humans

KW - inflammation

KW - interleukin-1beta

KW - leukocytes, mononuclear

KW - macrophages

KW - mice

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JO - The journal of infectious diseases

JF - The journal of infectious diseases

SN - 0022-1899

IS - 7

ER -