The Role of Dectin-2 for Host Defense Against Disseminated Candidiasis

Daniela C. Ifrim; Jessica Quintin; Flavie Courjol; Ineke Verschueren; J. Han van Krieken; Frank Koentgen; Chantal Fradin; Neil A. R. Gow; Leo A. B. Joosten; Jos W. M. van der Meer; Frank van de Veerdonk; Mihai G. Netea

doi:10.1089/jir.2015.0040

The Role of Dectin-2 for Host Defense Against Disseminated Candidiasis

Daniela C. Ifrim, Jessica Quintin, Flavie Courjol, Ineke Verschueren, J. Han van Krieken, Frank Koentgen, Chantal Fradin, Neil A. R. Gow, Leo A. B. Joosten, Jos W. M. van der Meer, Frank van de Veerdonk, Mihai G. Netea

Medical Sciences

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Abstract

Despite the fact that Candida albicans is an important human fungal pathogen and Dectin-2 is a major pattern recognition receptor for fungi, our knowledge regarding the role of Dectin-2 for the host defense against disseminated candidiasis is limited. Dectin-2 deficient (Dectin-2(-/-)) mice were more susceptible to systemic candidiasis, and the susceptibility was mirrored by an elevated fungal load in the kidneys that correlated with the presence of large inflammatory foci. Phagocytosis of Candida by the macrophages lacking the Dectin-2 receptor was moderately decreased, while production of most of the macrophage-derived cytokines from Dectin-2(-/-) mice with systemic candidiasis was decreased. No striking differences among several Candida mutants defective in mannans could be detected between naïve wild-type and Dectin-2(-/-) mice, apart from the β-mannan-deficient bmt1Δ/bmt2Δ/bmt5Δ triple mutant, suggesting that β-mannan may partially mask α-mannan detection, which is the major fungal structure recognized by Dectin-2. Deciphering the mechanisms responsible for host defense against the majority of C. albicans strains represents an important step in understanding the pathophysiology of systemic candidiasis, which might lead to the development of novel immunotherapeutic strategies.

Original language	English
Pages (from-to)	267-276
Number of pages	10
Journal	Journal of Interferon and Cytokine Research
Volume	36
Issue number	4
Early online date	27 Jan 2016
DOIs	https://doi.org/10.1089/jir.2015.0040
Publication status	Published - 5 Apr 2016

Bibliographical note

Acknowledgments
This work was supported by European Union ALLFUN (FP7/2007 2013, HEALTH-2010-260338) (Fungi in the setting of inflammation, allergy and autoimmune diseases: Translating basic science into clinical practices ‘‘ALLFUN’’) to D.C.I., F.C., C.F., M.G.N., and N.A.R.G. M.G.N and J.Q. were supported by a Vici grant of The Netherlands Organization of Scientific Research (to M.G.N.). M.G.N. was supported by an ERC Consolidator Grant (nr. 310372). N.A.R.G. was also supported by the Wellcome Trust (086827, 075470, 097377, & 101873).

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The Role of Dectin-2 for Host Defense Against Disseminated Candidiasis
ª Daniela C. Ifrim et al. 2016; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.
Final published version, 863 KBLicence: CC BY

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Ifrim, D. C., Quintin, J., Courjol, F., Verschueren, I., van Krieken, J. H., Koentgen, F., Fradin, C., Gow, N. A. R., Joosten, L. A. B., van der Meer, J. W. M., van de Veerdonk, F., & Netea, M. G. (2016). The Role of Dectin-2 for Host Defense Against Disseminated Candidiasis. Journal of Interferon and Cytokine Research, 36(4), 267-276. https://doi.org/10.1089/jir.2015.0040

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title = "The Role of Dectin-2 for Host Defense Against Disseminated Candidiasis",

abstract = "Despite the fact that Candida albicans is an important human fungal pathogen and Dectin-2 is a major pattern recognition receptor for fungi, our knowledge regarding the role of Dectin-2 for the host defense against disseminated candidiasis is limited. Dectin-2 deficient (Dectin-2(-/-)) mice were more susceptible to systemic candidiasis, and the susceptibility was mirrored by an elevated fungal load in the kidneys that correlated with the presence of large inflammatory foci. Phagocytosis of Candida by the macrophages lacking the Dectin-2 receptor was moderately decreased, while production of most of the macrophage-derived cytokines from Dectin-2(-/-) mice with systemic candidiasis was decreased. No striking differences among several Candida mutants defective in mannans could be detected between na{\"i}ve wild-type and Dectin-2(-/-) mice, apart from the β-mannan-deficient bmt1Δ/bmt2Δ/bmt5Δ triple mutant, suggesting that β-mannan may partially mask α-mannan detection, which is the major fungal structure recognized by Dectin-2. Deciphering the mechanisms responsible for host defense against the majority of C. albicans strains represents an important step in understanding the pathophysiology of systemic candidiasis, which might lead to the development of novel immunotherapeutic strategies.",

author = "Ifrim, {Daniela C.} and Jessica Quintin and Flavie Courjol and Ineke Verschueren and {van Krieken}, {J. Han} and Frank Koentgen and Chantal Fradin and Gow, {Neil A. R.} and Joosten, {Leo A. B.} and {van der Meer}, {Jos W. M.} and {van de Veerdonk}, Frank and Netea, {Mihai G.}",

note = "Acknowledgments This work was supported by European Union ALLFUN (FP7/2007 2013, HEALTH-2010-260338) (Fungi in the setting of inflammation, allergy and autoimmune diseases: Translating basic science into clinical practices {\textquoteleft}{\textquoteleft}ALLFUN{\textquoteright}{\textquoteright}) to D.C.I., F.C., C.F., M.G.N., and N.A.R.G. M.G.N and J.Q. were supported by a Vici grant of The Netherlands Organization of Scientific Research (to M.G.N.). M.G.N. was supported by an ERC Consolidator Grant (nr. 310372). N.A.R.G. was also supported by the Wellcome Trust (086827, 075470, 097377, & 101873).",

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AU - van Krieken, J. Han

AU - Koentgen, Frank

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AU - van der Meer, Jos W. M.

AU - van de Veerdonk, Frank

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N1 - Acknowledgments This work was supported by European Union ALLFUN (FP7/2007 2013, HEALTH-2010-260338) (Fungi in the setting of inflammation, allergy and autoimmune diseases: Translating basic science into clinical practices ‘‘ALLFUN’’) to D.C.I., F.C., C.F., M.G.N., and N.A.R.G. M.G.N and J.Q. were supported by a Vici grant of The Netherlands Organization of Scientific Research (to M.G.N.). M.G.N. was supported by an ERC Consolidator Grant (nr. 310372). N.A.R.G. was also supported by the Wellcome Trust (086827, 075470, 097377, & 101873).

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N2 - Despite the fact that Candida albicans is an important human fungal pathogen and Dectin-2 is a major pattern recognition receptor for fungi, our knowledge regarding the role of Dectin-2 for the host defense against disseminated candidiasis is limited. Dectin-2 deficient (Dectin-2(-/-)) mice were more susceptible to systemic candidiasis, and the susceptibility was mirrored by an elevated fungal load in the kidneys that correlated with the presence of large inflammatory foci. Phagocytosis of Candida by the macrophages lacking the Dectin-2 receptor was moderately decreased, while production of most of the macrophage-derived cytokines from Dectin-2(-/-) mice with systemic candidiasis was decreased. No striking differences among several Candida mutants defective in mannans could be detected between naïve wild-type and Dectin-2(-/-) mice, apart from the β-mannan-deficient bmt1Δ/bmt2Δ/bmt5Δ triple mutant, suggesting that β-mannan may partially mask α-mannan detection, which is the major fungal structure recognized by Dectin-2. Deciphering the mechanisms responsible for host defense against the majority of C. albicans strains represents an important step in understanding the pathophysiology of systemic candidiasis, which might lead to the development of novel immunotherapeutic strategies.

AB - Despite the fact that Candida albicans is an important human fungal pathogen and Dectin-2 is a major pattern recognition receptor for fungi, our knowledge regarding the role of Dectin-2 for the host defense against disseminated candidiasis is limited. Dectin-2 deficient (Dectin-2(-/-)) mice were more susceptible to systemic candidiasis, and the susceptibility was mirrored by an elevated fungal load in the kidneys that correlated with the presence of large inflammatory foci. Phagocytosis of Candida by the macrophages lacking the Dectin-2 receptor was moderately decreased, while production of most of the macrophage-derived cytokines from Dectin-2(-/-) mice with systemic candidiasis was decreased. No striking differences among several Candida mutants defective in mannans could be detected between naïve wild-type and Dectin-2(-/-) mice, apart from the β-mannan-deficient bmt1Δ/bmt2Δ/bmt5Δ triple mutant, suggesting that β-mannan may partially mask α-mannan detection, which is the major fungal structure recognized by Dectin-2. Deciphering the mechanisms responsible for host defense against the majority of C. albicans strains represents an important step in understanding the pathophysiology of systemic candidiasis, which might lead to the development of novel immunotherapeutic strategies.

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DO - 10.1089/jir.2015.0040

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JO - Journal of Interferon and Cytokine Research

JF - Journal of Interferon and Cytokine Research

IS - 4

ER -

The Role of Dectin-2 for Host Defense Against Disseminated Candidiasis

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