The role of Dectin-2 for host defense against systemic infection with Candida glabrata

Daniela C. Ifrim, Judith M. Bain, Delyth M. Reid, Marije Oostinga, Ineke Verschueren, Neil A. R. Gow, J. Han van Krieken, Gordon D. Brown, Bart-Jan Kullberg, Leo A B Joosten, Jos W. M. van der Meer, Frank Koentgen, Lars P. Erwig, Jessica Quintin, Mihai G. Netea

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Abstract

Although Candida glabrata is an important pathogenic Candida species, relatively little is known about its innate immune recognition. Here we explore the potential role of Dectin-2 for host defense against C. glabrata. Dectin-2-deficient (Dectin-2-/-) mice were found to be more susceptible to C. glabrata infections, showing a defective fungal clearance in kidneys, but not in the liver. The increased susceptibility to infection was accompanied by lower production of T helper 1 (Th1) and Th17-derived cytokines by splenocytes of Dectin-2-/- mice, while macrophage-derived cytokines were less affected. These defects were associated with a moderate, yet significant, decreased phagocytosis of the fungus by the Dectin-2-/- macrophages and neutrophils. Neutrophils of Dectin-2-/- mice also displayed a lower production of reactive oxygen species (ROS) upon challenge with opsonized C. glabrata or C. albicans. This study suggests that Dectin-2 is important in host defense against C. glabrata and provides new insights in the host defense mechanisms against this important fungal pathogen.
Original languageEnglish
Pages (from-to)1064-1073
Number of pages10
JournalInfection and Immunity
Volume82
Issue number3
Early online date16 Dec 2013
DOIs
Publication statusPublished - Mar 2014

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Candida glabrata
Infection
Neutrophils
Macrophages
Cytokines
mouse dectin-2
Candida
Phagocytosis
Reactive Oxygen Species
Fungi
Kidney
Liver

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The role of Dectin-2 for host defense against systemic infection with Candida glabrata. / Ifrim, Daniela C. ; Bain, Judith M.; Reid, Delyth M.; Oostinga, Marije; Verschueren, Ineke; Gow, Neil A. R.; van Krieken, J. Han; Brown, Gordon D.; Kullberg, Bart-Jan; Joosten, Leo A B; van der Meer, Jos W. M.; Koentgen, Frank; Erwig, Lars P.; Quintin, Jessica; Netea, Mihai G.

In: Infection and Immunity, Vol. 82, No. 3, 03.2014, p. 1064-1073.

Research output: Contribution to journalArticle

Ifrim, DC, Bain, JM, Reid, DM, Oostinga, M, Verschueren, I, Gow, NAR, van Krieken, JH, Brown, GD, Kullberg, B-J, Joosten, LAB, van der Meer, JWM, Koentgen, F, Erwig, LP, Quintin, J & Netea, MG 2014, 'The role of Dectin-2 for host defense against systemic infection with Candida glabrata', Infection and Immunity, vol. 82, no. 3, pp. 1064-1073. https://doi.org/10.1128/IAI.01189-13
Ifrim, Daniela C. ; Bain, Judith M. ; Reid, Delyth M. ; Oostinga, Marije ; Verschueren, Ineke ; Gow, Neil A. R. ; van Krieken, J. Han ; Brown, Gordon D. ; Kullberg, Bart-Jan ; Joosten, Leo A B ; van der Meer, Jos W. M. ; Koentgen, Frank ; Erwig, Lars P. ; Quintin, Jessica ; Netea, Mihai G. / The role of Dectin-2 for host defense against systemic infection with Candida glabrata. In: Infection and Immunity. 2014 ; Vol. 82, No. 3. pp. 1064-1073.
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abstract = "Although Candida glabrata is an important pathogenic Candida species, relatively little is known about its innate immune recognition. Here we explore the potential role of Dectin-2 for host defense against C. glabrata. Dectin-2-deficient (Dectin-2-/-) mice were found to be more susceptible to C. glabrata infections, showing a defective fungal clearance in kidneys, but not in the liver. The increased susceptibility to infection was accompanied by lower production of T helper 1 (Th1) and Th17-derived cytokines by splenocytes of Dectin-2-/- mice, while macrophage-derived cytokines were less affected. These defects were associated with a moderate, yet significant, decreased phagocytosis of the fungus by the Dectin-2-/- macrophages and neutrophils. Neutrophils of Dectin-2-/- mice also displayed a lower production of reactive oxygen species (ROS) upon challenge with opsonized C. glabrata or C. albicans. This study suggests that Dectin-2 is important in host defense against C. glabrata and provides new insights in the host defense mechanisms against this important fungal pathogen.",
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note = "We thank A. Whittington for the useful discussion and H. M. J. Roelofs and E. D. Olthof for the assistance with ROS production. We thank the University of Aberdeen Animal Facility and Microscopy Facility and also D. MacCallum and R. Drummond for technical assistance. 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., M.G.N., and N.A.R.G. M.G.N and J.Q. were also supported by a Vici grant of the Netherlands Organization of Scientific Research (to M.G.N.). N.A.R.G. was also supported by the Wellcome Trust (080088, 086827, 075470, and 097377). L.P.E. is a CSO Senior Clinical Fellow and supported by WT project, programme, and equipment grants (089930 and 094847). G.D.B. was funded by the Wellcome Trust (086558 and 097377).",
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AU - Bain, Judith M.

AU - Reid, Delyth M.

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AU - Verschueren, Ineke

AU - Gow, Neil A. R.

AU - van Krieken, J. Han

AU - Brown, Gordon D.

AU - Kullberg, Bart-Jan

AU - Joosten, Leo A B

AU - van der Meer, Jos W. M.

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AU - Quintin, Jessica

AU - Netea, Mihai G.

N1 - We thank A. Whittington for the useful discussion and H. M. J. Roelofs and E. D. Olthof for the assistance with ROS production. We thank the University of Aberdeen Animal Facility and Microscopy Facility and also D. MacCallum and R. Drummond for technical assistance. 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., M.G.N., and N.A.R.G. M.G.N and J.Q. were also supported by a Vici grant of the Netherlands Organization of Scientific Research (to M.G.N.). N.A.R.G. was also supported by the Wellcome Trust (080088, 086827, 075470, and 097377). L.P.E. is a CSO Senior Clinical Fellow and supported by WT project, programme, and equipment grants (089930 and 094847). G.D.B. was funded by the Wellcome Trust (086558 and 097377).

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N2 - Although Candida glabrata is an important pathogenic Candida species, relatively little is known about its innate immune recognition. Here we explore the potential role of Dectin-2 for host defense against C. glabrata. Dectin-2-deficient (Dectin-2-/-) mice were found to be more susceptible to C. glabrata infections, showing a defective fungal clearance in kidneys, but not in the liver. The increased susceptibility to infection was accompanied by lower production of T helper 1 (Th1) and Th17-derived cytokines by splenocytes of Dectin-2-/- mice, while macrophage-derived cytokines were less affected. These defects were associated with a moderate, yet significant, decreased phagocytosis of the fungus by the Dectin-2-/- macrophages and neutrophils. Neutrophils of Dectin-2-/- mice also displayed a lower production of reactive oxygen species (ROS) upon challenge with opsonized C. glabrata or C. albicans. This study suggests that Dectin-2 is important in host defense against C. glabrata and provides new insights in the host defense mechanisms against this important fungal pathogen.

AB - Although Candida glabrata is an important pathogenic Candida species, relatively little is known about its innate immune recognition. Here we explore the potential role of Dectin-2 for host defense against C. glabrata. Dectin-2-deficient (Dectin-2-/-) mice were found to be more susceptible to C. glabrata infections, showing a defective fungal clearance in kidneys, but not in the liver. The increased susceptibility to infection was accompanied by lower production of T helper 1 (Th1) and Th17-derived cytokines by splenocytes of Dectin-2-/- mice, while macrophage-derived cytokines were less affected. These defects were associated with a moderate, yet significant, decreased phagocytosis of the fungus by the Dectin-2-/- macrophages and neutrophils. Neutrophils of Dectin-2-/- mice also displayed a lower production of reactive oxygen species (ROS) upon challenge with opsonized C. glabrata or C. albicans. This study suggests that Dectin-2 is important in host defense against C. glabrata and provides new insights in the host defense mechanisms against this important fungal pathogen.

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