Dependence on Mincle and Dectin-2 Varies With Multiple Candida Species During Systemic Infection

Aiysha Thompson; Diogo M da Fonseca; Louise Walker; James S Griffiths; Philip R Taylor; Neil A R Gow; Selinda J Orr

doi:10.3389/fmicb.2021.633229

Dependence on Mincle and Dectin-2 Varies With Multiple Candida Species During Systemic Infection

Aiysha Thompson, Diogo M da Fonseca, Louise Walker, James S Griffiths, Philip R Taylor, Neil A R Gow, Selinda J Orr^* (Corresponding Author)

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

More than 95% of invasive Candida infections are caused by four Candida spp. (C. albicans, C. glabrata, C. tropicalis, C. parapsilosis). C-type lectin-like receptors (CLRs), such as Dectin-1, Dectin-2, and Mincle mediate immune responses to C. albicans. Dectin-1 promotes clearance of C. albicans, C. glabrata, C. tropicalis, and C. parapsilosis, however, dependence on Dectin-1 for specific immune responses varies with the different Candida spp. Dectin-2 is important for host immunity to C. albicans and C. glabrata, and Mincle is important for the immune response to C. albicans. However, whether Dectin-2 drives host immunity to C. tropicalis or C. parapsilosis, and whether Mincle mediates host immunity to C. glabrata, C. tropicalis or C. parapsilosis is unknown. Therefore, we compared the roles of Dectin-2 and Mincle in response to these four Candida spp. We demonstrate that these four Candida spp. cell walls have differential mannan contents. Mincle and Dectin-2 play a key role in regulating cytokine production in response to these four Candida spp. and Dectin-2 is also important for clearance of all four Candida spp. during systemic infection. However, Mincle was only important for clearance of C. tropicalis during systemic infection. Our data indicate that multiple Candida spp. have different mannan contents, and dependence on the mannan-detecting CLRs, Mincle, and Dectin-2 varies between different Candida spp. during systemic infection.

Original language	English
Article number	633229
Number of pages	13
Journal	Frontiers in Microbiology
Volume	12
DOIs	https://doi.org/10.3389/fmicb.2021.633229
Publication status	Published - 25 Feb 2021

Bibliographical note

FUNDING
SO was supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant No. 099953/Z/12/Z) and by a Wellcome Trust Cross-Disciplinary Award. NG acknowledges Wellcome Trust support of a Senior Investigator (101873/Z/13/Z), Collaborative (200208/A/15/Z) and Strategic Awards (097377/Z11/Z) and the MRC Centre for Medical Mycology (MR/N006364/2). PT was funded by a Wellcome Trust Investigator Award (107964/Z/15/Z) and the UK Dementia Research Institute.

ACKNOWLEDGMENTS
We wish to acknowledge the NIH-sponsored Mutant Mouse Regional Resource Center (MMRRC) National System as the source of genetically altered mice (C57BL/6-Clec4et m1. 1C fg /Mmucd 031936-UCD) for use in this study. The mice were produced and deposited to the MMRRC by the Consortium for Functional Glycomics supported by the National Institute of General Medical Sciences (GM62116). We also thank the Microscopy and Histology Core Facility at the University of Aberdeen for expert assistance with TEM.

Keywords

CLR
Candida
Dectin-2
Mincle
fungal

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Cite this

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title = "Dependence on Mincle and Dectin-2 Varies With Multiple Candida Species During Systemic Infection",

abstract = "More than 95% of invasive Candida infections are caused by four Candida spp. (C. albicans, C. glabrata, C. tropicalis, C. parapsilosis). C-type lectin-like receptors (CLRs), such as Dectin-1, Dectin-2, and Mincle mediate immune responses to C. albicans. Dectin-1 promotes clearance of C. albicans, C. glabrata, C. tropicalis, and C. parapsilosis, however, dependence on Dectin-1 for specific immune responses varies with the different Candida spp. Dectin-2 is important for host immunity to C. albicans and C. glabrata, and Mincle is important for the immune response to C. albicans. However, whether Dectin-2 drives host immunity to C. tropicalis or C. parapsilosis, and whether Mincle mediates host immunity to C. glabrata, C. tropicalis or C. parapsilosis is unknown. Therefore, we compared the roles of Dectin-2 and Mincle in response to these four Candida spp. We demonstrate that these four Candida spp. cell walls have differential mannan contents. Mincle and Dectin-2 play a key role in regulating cytokine production in response to these four Candida spp. and Dectin-2 is also important for clearance of all four Candida spp. during systemic infection. However, Mincle was only important for clearance of C. tropicalis during systemic infection. Our data indicate that multiple Candida spp. have different mannan contents, and dependence on the mannan-detecting CLRs, Mincle, and Dectin-2 varies between different Candida spp. during systemic infection.",

keywords = "CLR, Candida, Dectin-2, Mincle, fungal",

author = "Aiysha Thompson and {da Fonseca}, {Diogo M} and Louise Walker and Griffiths, {James S} and Taylor, {Philip R} and Gow, {Neil A R} and Orr, {Selinda J}",

note = "FUNDING SO was supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant No. 099953/Z/12/Z) and by a Wellcome Trust Cross-Disciplinary Award. NG acknowledges Wellcome Trust support of a Senior Investigator (101873/Z/13/Z), Collaborative (200208/A/15/Z) and Strategic Awards (097377/Z11/Z) and the MRC Centre for Medical Mycology (MR/N006364/2). PT was funded by a Wellcome Trust Investigator Award (107964/Z/15/Z) and the UK Dementia Research Institute. ACKNOWLEDGMENTS We wish to acknowledge the NIH-sponsored Mutant Mouse Regional Resource Center (MMRRC) National System as the source of genetically altered mice (C57BL/6-Clec4et m1. 1C fg /Mmucd 031936-UCD) for use in this study. The mice were produced and deposited to the MMRRC by the Consortium for Functional Glycomics supported by the National Institute of General Medical Sciences (GM62116). We also thank the Microscopy and Histology Core Facility at the University of Aberdeen for expert assistance with TEM.",

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AU - Taylor, Philip R

AU - Gow, Neil A R

AU - Orr, Selinda J

N1 - FUNDING SO was supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant No. 099953/Z/12/Z) and by a Wellcome Trust Cross-Disciplinary Award. NG acknowledges Wellcome Trust support of a Senior Investigator (101873/Z/13/Z), Collaborative (200208/A/15/Z) and Strategic Awards (097377/Z11/Z) and the MRC Centre for Medical Mycology (MR/N006364/2). PT was funded by a Wellcome Trust Investigator Award (107964/Z/15/Z) and the UK Dementia Research Institute. ACKNOWLEDGMENTS We wish to acknowledge the NIH-sponsored Mutant Mouse Regional Resource Center (MMRRC) National System as the source of genetically altered mice (C57BL/6-Clec4et m1. 1C fg /Mmucd 031936-UCD) for use in this study. The mice were produced and deposited to the MMRRC by the Consortium for Functional Glycomics supported by the National Institute of General Medical Sciences (GM62116). We also thank the Microscopy and Histology Core Facility at the University of Aberdeen for expert assistance with TEM.

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N2 - More than 95% of invasive Candida infections are caused by four Candida spp. (C. albicans, C. glabrata, C. tropicalis, C. parapsilosis). C-type lectin-like receptors (CLRs), such as Dectin-1, Dectin-2, and Mincle mediate immune responses to C. albicans. Dectin-1 promotes clearance of C. albicans, C. glabrata, C. tropicalis, and C. parapsilosis, however, dependence on Dectin-1 for specific immune responses varies with the different Candida spp. Dectin-2 is important for host immunity to C. albicans and C. glabrata, and Mincle is important for the immune response to C. albicans. However, whether Dectin-2 drives host immunity to C. tropicalis or C. parapsilosis, and whether Mincle mediates host immunity to C. glabrata, C. tropicalis or C. parapsilosis is unknown. Therefore, we compared the roles of Dectin-2 and Mincle in response to these four Candida spp. We demonstrate that these four Candida spp. cell walls have differential mannan contents. Mincle and Dectin-2 play a key role in regulating cytokine production in response to these four Candida spp. and Dectin-2 is also important for clearance of all four Candida spp. during systemic infection. However, Mincle was only important for clearance of C. tropicalis during systemic infection. Our data indicate that multiple Candida spp. have different mannan contents, and dependence on the mannan-detecting CLRs, Mincle, and Dectin-2 varies between different Candida spp. during systemic infection.

AB - More than 95% of invasive Candida infections are caused by four Candida spp. (C. albicans, C. glabrata, C. tropicalis, C. parapsilosis). C-type lectin-like receptors (CLRs), such as Dectin-1, Dectin-2, and Mincle mediate immune responses to C. albicans. Dectin-1 promotes clearance of C. albicans, C. glabrata, C. tropicalis, and C. parapsilosis, however, dependence on Dectin-1 for specific immune responses varies with the different Candida spp. Dectin-2 is important for host immunity to C. albicans and C. glabrata, and Mincle is important for the immune response to C. albicans. However, whether Dectin-2 drives host immunity to C. tropicalis or C. parapsilosis, and whether Mincle mediates host immunity to C. glabrata, C. tropicalis or C. parapsilosis is unknown. Therefore, we compared the roles of Dectin-2 and Mincle in response to these four Candida spp. We demonstrate that these four Candida spp. cell walls have differential mannan contents. Mincle and Dectin-2 play a key role in regulating cytokine production in response to these four Candida spp. and Dectin-2 is also important for clearance of all four Candida spp. during systemic infection. However, Mincle was only important for clearance of C. tropicalis during systemic infection. Our data indicate that multiple Candida spp. have different mannan contents, and dependence on the mannan-detecting CLRs, Mincle, and Dectin-2 varies between different Candida spp. during systemic infection.

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KW - Dectin-2

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Dependence on Mincle and Dectin-2 Varies With Multiple Candida Species During Systemic Infection

Abstract

Bibliographical note

Keywords

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