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

doi:10.1128/IAI.01189-13

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 language	English
Pages (from-to)	1064-1073
Number of pages	10
Journal	Infection and Immunity
Volume	82
Issue number	3
Early online date	16 Dec 2013
DOIs	https://doi.org/10.1128/IAI.01189-13
Publication status	Published - Mar 2014

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Ifrim, D. C., Bain, J. M., Reid, D. M., Oostinga, M., Verschueren, I., Gow, N. A. R., ... Netea, M. G. (2014). The role of Dectin-2 for host defense against systemic infection with Candida glabrata. Infection and Immunity, 82(3), 1064-1073. https://doi.org/10.1128/IAI.01189-13

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 journal › Article

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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title = "The role of Dectin-2 for host defense against systemic infection with Candida glabrata",

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.",

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

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.

AU - Oostinga, Marije

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.

AU - Koentgen, Frank

AU - Erwig, Lars P.

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).

PY - 2014/3

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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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DO - 10.1128/IAI.01189-13

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JO - Infection and Immunity

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SN - 0019-9567

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10.1128/IAI.01189-13

Role of Dectin-2 for Host Defense against Systemic Infection with Candida glabrata
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/3.0/
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