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Article ; Online: Detailed characterisation of invasive aspergillosis in a murine model of X-linked chronic granulomatous disease shows new insights in infections caused by

King, Jill / Dambuza, Ivy M / Reid, Delyth M / Yuecel, Raif / Brown, Gordon D / Warris, Adilia

Frontiers in cellular and infection microbiology

2023 Volume 13, Page(s) 1241770

Abstract: Introduction: Invasive aspergillosis (IA) is the most prevalent infectious complication in patients with chronic granulomatous disease (CGD). Yet, understanding of fungal pathogenesis in the CGD host remains limited, particularly with regards to : ... ...

Abstract	Introduction: Invasive aspergillosis (IA) is the most prevalent infectious complication in patients with chronic granulomatous disease (CGD). Yet, understanding of fungal pathogenesis in the CGD host remains limited, particularly with regards to Methods: We have used a murine model of X-linked CGD to investigate how the pathogenesis of IA varies between Results: We observed a lack of association between pulmonary pathology and infection outcome in gp91 Conclusion: We have provided an in-depth characterisation of the immune response to pulmonary aspergillosis in an X-linked CGD murine model. This provides the first description of distinct pulmonary inflammatory environments in
MeSH term(s)	Animals ; Mice ; Mice, Inbred C57BL ; Aspergillus fumigatus/genetics ; Aspergillus nidulans/genetics ; Granulomatous Disease, Chronic/complications ; Disease Models, Animal ; Aspergillosis ; Invasive Fungal Infections ; Cytokines
Chemical Substances	Cytokines
Language	English
Publishing date	2023-09-01
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2023.1241770
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Article ; Online: The Rab32/BLOC-3-dependent pathway mediates host defense against different pathogens in human macrophages.

Baldassarre, Massimiliano / Solano-Collado, Virtu / Balci, Arda / Colamarino, Rosa A / Dambuza, Ivy M / Reid, Delyth M / Wilson, Heather M / Brown, Gordon D / Mukhopadhyay, Subhankar / Dougan, Gordon / Spanò, Stefania

Science advances

2021 Volume 7, Issue 3

Abstract: Macrophages provide a first line of defense against microorganisms, and while some mechanisms to kill pathogens such as the oxidative burst are well described, others are still undefined or unknown. Here, we report that the Rab32 guanosine triphosphatase ...

Abstract	Macrophages provide a first line of defense against microorganisms, and while some mechanisms to kill pathogens such as the oxidative burst are well described, others are still undefined or unknown. Here, we report that the Rab32 guanosine triphosphatase and its guanine nucleotide exchange factor BLOC-3 (biogenesis of lysosome-related organelles complex-3) are central components of a trafficking pathway that controls both bacterial and fungal intracellular pathogens. This host-defense mechanism is active in both human and murine macrophages and is independent of well-known antimicrobial mechanisms such as the NADPH (reduced form of nicotinamide adenine dinucleotide phosphate)-dependent oxidative burst, production of nitric oxide, and antimicrobial peptides. To survive in human macrophages,
MeSH term(s)	Animals ; Guanine Nucleotide Exchange Factors/metabolism ; Humans ; Lysosomes/metabolism ; Macrophages/metabolism ; Mammals/metabolism ; Mice ; Salmonella typhi ; rab GTP-Binding Proteins/metabolism
Chemical Substances	Guanine Nucleotide Exchange Factors ; Rab32 protein, human (EC 3.6.1.-) ; Rab32 protein, mouse (EC 3.6.1.-) ; rab GTP-Binding Proteins (EC 3.6.5.2)
Language	English
Publishing date	2021-01-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.abb1795
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Article ; Online: Treatment With FoxP3+ Antigen-Experienced T Regulatory Cells Arrests Progressive Retinal Damage in a Spontaneous Model of Uveitis.

Liu, Yi-Hsia / Mölzer, Christine / Makinen, Kimmo / Kamoi, Koju / Corbett, Clare L C / Klaska, Izabela P / Reid, Delyth M / Wilson, Heather M / Kuffová, Lucia / Cornall, Richard J / Forrester, John V

Frontiers in immunology

2020 Volume 11, Page(s) 2071

Abstract: We specify the clinical features of a spontaneous experimental autoimmune uveitis (EAU) model, in which foreign hen-egg lysozyme (HEL) is expressed in the retina, controlled by the promoter for interphotoreceptor retinol binding protein (IRBP). We ... ...

Abstract	We specify the clinical features of a spontaneous experimental autoimmune uveitis (EAU) model, in which foreign hen-egg lysozyme (HEL) is expressed in the retina, controlled by the promoter for interphotoreceptor retinol binding protein (IRBP). We previously reported 100% P21 (post-partum day) IRBP:HEL single transgenic (sTg) mice, when crossed to transgenic T cell receptor mice (3A9) generating the double transgenic (dTg) genotype, develop EAU despite profound lymphopenia (thymic HEL-specific T cell deletion). In this work, we characterized the immune component of this model and found conventional dTg CD4+ T cells were less anergic than those from 3A9 controls. Furthermore, prior
MeSH term(s)	Animals ; Autoimmune Diseases/immunology ; Cells, Cultured ; Disease Models, Animal ; Eye Proteins/immunology ; Forkhead Transcription Factors/metabolism ; Humans ; Immune Tolerance ; Immunotherapy, Adoptive/methods ; Interleukin-2 Receptor alpha Subunit/metabolism ; Mice ; Mice, Transgenic ; Retina/pathology ; Retinol-Binding Proteins/immunology ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/transplantation ; Uveitis/immunology
Chemical Substances	Eye Proteins ; Forkhead Transcription Factors ; Foxp3 protein, mouse ; Interleukin-2 Receptor alpha Subunit ; Retinol-Binding Proteins ; interstitial retinol-binding protein
Language	English
Publishing date	2020-09-04
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.02071
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Article ; Online: Detection of IL-36γ through noninvasive tape stripping reliably discriminates psoriasis from atopic eczema.

Berekméri, Anna / Latzko, Anne / Alase, Adewonuola / Macleod, Tom / Ainscough, Joseph S / Laws, Philip / Goodfield, Mark / Wright, Andrew / Helliwell, Philip / Edward, Sara / Brown, Gordon D / Reid, Delyth M / Wenzel, Joerg / Stacey, Martin / Wittmann, Miriam

The Journal of allergy and clinical immunology

2018 Volume 142, Issue 3, Page(s) 988–991.e4

MeSH term(s)	Adolescent ; Adult ; Aged ; Animals ; Antibodies, Monoclonal/immunology ; Eczema/diagnosis ; Eczema/immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Interleukin-1/immunology ; Male ; Mice, Inbred C57BL ; Middle Aged ; Psoriasis/diagnosis ; Psoriasis/immunology ; Rats, Sprague-Dawley ; Sensitivity and Specificity ; Surgical Tape ; Young Adult
Chemical Substances	Antibodies, Monoclonal ; IL36G protein, human ; Interleukin-1
Language	English
Publishing date	2018-05-18
Publishing country	United States
Document type	Case Reports ; Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2018.04.031
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Article ; Online: The pattern recognition receptors dectin-2, mincle, and FcRγ impact the dynamics of phagocytosis of Candida, Saccharomyces, Malassezia, and Mucor species.

Haider, Mohammed / Dambuza, Ivy M / Asamaphan, Patawee / Stappers, Mark / Reid, Delyth / Yamasaki, Sho / Brown, Gordon D / Gow, Neil A R / Erwig, Lars P

PloS one

2019 Volume 14, Issue 8, Page(s) e0220867

Abstract: Phagocytosis is a receptor-mediated process critical to innate immune clearance of pathogens. It proceeds in a regulated sequence of stages: (a) migration of phagocytes towards pathogens, (b) recognition of PAMPs and binding through PRRs, (c) engulfment ... ...

Abstract	Phagocytosis is a receptor-mediated process critical to innate immune clearance of pathogens. It proceeds in a regulated sequence of stages: (a) migration of phagocytes towards pathogens, (b) recognition of PAMPs and binding through PRRs, (c) engulfment and internalisation into phagosomes, (d) phagosome maturation, and (e) killing of pathogen or host cells. However, little is known about the role that individual receptors play in these discrete stages in the recognition of fungal cells. In a previous study, we found that dectin-2 deficiency impacted some but not all stages of macrophage-mediated phagocytosis of Candida glabrata. Because the C-type lectin receptor dectin-2 critically requires coupling to the FcRγ chain for signalling, we hypothesised that this coupling may be important for regulating phagocytosis of fungal cargo. We therefore examined how deficiency in FcRγ itself or two receptors to which it couples (dectin-2 and mincle) impacts phagocytosis of six fungal organisms representing three different fungal taxa. Our data show that deficiency in these proteins impairs murine bone marrow-derived macrophage migration, engulfment, and phagosome maturation, but not macrophage survival. Therefore, FcRγ engagement with selective C-type lectin receptors (CLRs) critically affects the spatio-temporal dynamics of fungal phagocytosis.
MeSH term(s)	Animals ; Candida/immunology ; Cell Movement ; Fungi/immunology ; Lectins, C-Type/immunology ; Lectins, C-Type/metabolism ; Macrophages/cytology ; Malassezia/immunology ; Membrane Proteins/immunology ; Membrane Proteins/metabolism ; Mice ; Mucor/immunology ; Phagocytosis ; Protein Binding ; Receptors, Fc/immunology ; Receptors, Fc/metabolism ; Receptors, Pattern Recognition/immunology ; Receptors, Pattern Recognition/metabolism ; Saccharomyces/immunology
Chemical Substances	Clecsf8 protein, mouse ; Lectins, C-Type ; Membrane Proteins ; Receptors, Fc ; Receptors, Pattern Recognition ; dectin-2, mouse
Language	English
Publishing date	2019-08-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0220867
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Article ; Online: The pattern recognition receptors dectin-2, mincle, and FcRγ impact the dynamics of phagocytosis of Candida, Saccharomyces, Malassezia, and Mucor species.

Mohammed Haider / Ivy M Dambuza / Patawee Asamaphan / Mark Stappers / Delyth Reid / Sho Yamasaki / Gordon D Brown / Neil A R Gow / Lars P Erwig

PLoS ONE, Vol 14, Iss 8, p e

2019 Volume 0220867

Abstract	Phagocytosis is a receptor-mediated process critical to innate immune clearance of pathogens. It proceeds in a regulated sequence of stages: (a) migration of phagocytes towards pathogens, (b) recognition of PAMPs and binding through PRRs, (c) engulfment and internalisation into phagosomes, (d) phagosome maturation, and (e) killing of pathogen or host cells. However, little is known about the role that individual receptors play in these discrete stages in the recognition of fungal cells. In a previous study, we found that dectin-2 deficiency impacted some but not all stages of macrophage-mediated phagocytosis of Candida glabrata. Because the C-type lectin receptor dectin-2 critically requires coupling to the FcRγ chain for signalling, we hypothesised that this coupling may be important for regulating phagocytosis of fungal cargo. We therefore examined how deficiency in FcRγ itself or two receptors to which it couples (dectin-2 and mincle) impacts phagocytosis of six fungal organisms representing three different fungal taxa. Our data show that deficiency in these proteins impairs murine bone marrow-derived macrophage migration, engulfment, and phagosome maturation, but not macrophage survival. Therefore, FcRγ engagement with selective C-type lectin receptors (CLRs) critically affects the spatio-temporal dynamics of fungal phagocytosis.
Keywords	Medicine ; R ; Science ; Q
Subject code	612
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article ; Online: Signalling through MyD88 drives surface expression of the mycobacterial receptors MCL (Clecsf8, Clec4d) and Mincle (Clec4e) following microbial stimulation.

Kerscher, Bernhard / Dambuza, Ivy M / Christofi, Maria / Reid, Delyth M / Yamasaki, Sho / Willment, Janet A / Brown, Gordon D

Microbes and infection

2016 Volume 18, Issue 7-8, Page(s) 505–509

Abstract: The heterodimeric mycobacterial receptors, macrophage C-type lectin (MCL) and macrophage inducible C-type lectin (Mincle), are upregulated at the cell surface following microbial challenge, but the mechanisms underlying this response are unclear. Here we ...

Abstract	The heterodimeric mycobacterial receptors, macrophage C-type lectin (MCL) and macrophage inducible C-type lectin (Mincle), are upregulated at the cell surface following microbial challenge, but the mechanisms underlying this response are unclear. Here we report that microbial stimulation triggers Mincle expression through the myeloid differentiation primary response gene 88 (MyD88) pathway; a process that does not require MCL. Conversely, we show that MCL is constitutively expressed but retained intracellularly until Mincle is induced, whereupon the receptors form heterodimers which are translocated to the cell surface. Thus this "two-step" model for induction of these key receptors provides new insights into the underlying mechanisms of anti-mycobacterial immunity.
MeSH term(s)	Animals ; Cells, Cultured ; Gene Expression ; Host-Pathogen Interactions ; Lectins, C-Type/genetics ; Lectins, C-Type/metabolism ; Macrophages/immunology ; Macrophages/microbiology ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mice, Inbred C57BL ; Mycobacterium/immunology ; Myeloid Differentiation Factor 88/metabolism ; Receptors, Cell Surface/genetics ; Receptors, Cell Surface/metabolism ; Receptors, Immunologic/genetics ; Receptors, Immunologic/metabolism
Chemical Substances	Clec4d protein, mouse ; Clecsf8 protein, mouse ; Lectins, C-Type ; Membrane Proteins ; Myd88 protein, mouse ; Myeloid Differentiation Factor 88 ; Receptors, Cell Surface ; Receptors, Immunologic
Language	English
Publishing date	2016-03-19
Publishing country	France
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1465093-9
ISSN	1769-714X ; 1286-4579
ISSN (online)	1769-714X
ISSN	1286-4579
DOI	10.1016/j.micinf.2016.03.007
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Article ; Online: Pattern recognition: recent insights from Dectin-1.

Reid, Delyth M / Gow, Neil A R / Brown, Gordon D

Current opinion in immunology

2009 Volume 21, Issue 1, Page(s) 30–37

Abstract: The beta-glucan receptor Dectin-1 is an archetypical non-toll-like pattern recognition receptor expressed predominantly by myeloid cells, which can induce its own intracellular signalling and can mediate a variety of cellular responses, such as cytokine ... ...

Abstract	The beta-glucan receptor Dectin-1 is an archetypical non-toll-like pattern recognition receptor expressed predominantly by myeloid cells, which can induce its own intracellular signalling and can mediate a variety of cellular responses, such as cytokine production. Recent identification of the components of these signalling pathways, such as Syk kinase, CARD9 and Raf-1, has provided novel insights into the molecular mechanisms underlying Dectin-1 function. Furthermore, a broader appreciation of the cellular responses mediated by this receptor and the effects of interactions with other receptors, including the TLRs, have greatly furthered our understanding of innate immunity and how this drives the development of adaptive immunity, particularly Th17 responses. Recent studies have highlighted the importance of Dectin-1 in anti-fungal immunity, in both mice and humans, and have suggested a possible involvement of this receptor in the control of mycobacterial infections.
MeSH term(s)	Animals ; CARD Signaling Adaptor Proteins/immunology ; CARD Signaling Adaptor Proteins/metabolism ; Humans ; Immunity, Cellular ; Immunity, Innate ; Interleukin-17/immunology ; Intracellular Signaling Peptides and Proteins/immunology ; Intracellular Signaling Peptides and Proteins/metabolism ; Lectins, C-Type ; Membrane Proteins/immunology ; Membrane Proteins/metabolism ; Mice ; Mycobacterium Infections/immunology ; Mycoses/immunology ; Myeloid Cells/immunology ; Myeloid Cells/metabolism ; Nerve Tissue Proteins/immunology ; Nerve Tissue Proteins/metabolism ; Protein-Tyrosine Kinases/immunology ; Protein-Tyrosine Kinases/metabolism ; Proto-Oncogene Proteins c-raf/immunology ; Proto-Oncogene Proteins c-raf/metabolism ; Signal Transduction ; Syk Kinase ; Th1 Cells/immunology ; Th1 Cells/metabolism ; Toll-Like Receptors/immunology ; Toll-Like Receptors/metabolism
Chemical Substances	CARD Signaling Adaptor Proteins ; CARD9 protein, human ; Interleukin-17 ; Intracellular Signaling Peptides and Proteins ; Lectins, C-Type ; Membrane Proteins ; Nerve Tissue Proteins ; Toll-Like Receptors ; dectin 1 ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; SYK protein, human (EC 2.7.10.2) ; Syk Kinase (EC 2.7.10.2) ; Syk protein, mouse (EC 2.7.10.2) ; Proto-Oncogene Proteins c-raf (EC 2.7.11.1)
Language	English
Publishing date	2009-02-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1035767-1
ISSN	1879-0372 ; 0952-7915
ISSN (online)	1879-0372
ISSN	0952-7915
DOI	10.1016/j.coi.2009.01.003
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Article ; Online: Microbiota Sensing by Mincle-Syk Axis in Dendritic Cells Regulates Interleukin-17 and -22 Production and Promotes Intestinal Barrier Integrity.

Martínez-López, María / Iborra, Salvador / Conde-Garrosa, Ruth / Mastrangelo, Annalaura / Danne, Camille / Mann, Elizabeth R / Reid, Delyth M / Gaboriau-Routhiau, Valérie / Chaparro, Maria / Lorenzo, María P / Minnerup, Lara / Saz-Leal, Paula / Slack, Emma / Kemp, Benjamin / Gisbert, Javier P / Dzionek, Andrzej / Robinson, Matthew J / Rupérez, Francisco J / Cerf-Bensussan, Nadine /

Brown, Gordon D / Bernardo, David / LeibundGut-Landmann, Salomé / Sancho, David

Immunity

2019 Volume 50, Issue 2, Page(s) 446–461.e9

Abstract: Production of interleukin-17 (IL-17) and IL-22 by T helper 17 (Th17) cells and group 3 innate lymphoid cells (ILC3s) in response to the gut microbiota ensures maintenance of intestinal barrier function. Here, we examined the mechanisms whereby the immune ...

Abstract	Production of interleukin-17 (IL-17) and IL-22 by T helper 17 (Th17) cells and group 3 innate lymphoid cells (ILC3s) in response to the gut microbiota ensures maintenance of intestinal barrier function. Here, we examined the mechanisms whereby the immune system detects microbiota in the steady state. A Syk-kinase-coupled signaling pathway in dendritic cells (DCs) was critical for commensal-dependent production of IL-17 and IL-22 by CD4
MeSH term(s)	Animals ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Gastrointestinal Microbiome/immunology ; Gastrointestinal Microbiome/physiology ; Humans ; Interleukin-17/immunology ; Interleukin-17/metabolism ; Interleukins/immunology ; Interleukins/metabolism ; Intestinal Mucosa/immunology ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/microbiology ; Lectins, C-Type/genetics ; Lectins, C-Type/immunology ; Lectins, C-Type/metabolism ; Membrane Proteins/genetics ; Membrane Proteins/immunology ; Membrane Proteins/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Peyer's Patches/immunology ; Peyer's Patches/metabolism ; Peyer's Patches/microbiology ; Signal Transduction/immunology ; Syk Kinase/genetics ; Syk Kinase/immunology ; Syk Kinase/metabolism ; Th17 Cells/immunology ; Th17 Cells/metabolism ; Interleukin-22
Chemical Substances	Clecsf8 protein, mouse ; Interleukin-17 ; Interleukins ; Lectins, C-Type ; Membrane Proteins ; Syk Kinase (EC 2.7.10.2)
Language	English
Publishing date	2019-01-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2018.12.020
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Article ; Online: Cutting edge: Failure of antigen-specific CD4+ T cell recruitment to the kidney during systemic candidiasis.

Drummond, Rebecca A / Wallace, Carol / Reid, Delyth M / Way, Sing Sing / Kaplan, Daniel H / Brown, Gordon D

Journal of immunology (Baltimore, Md. : 1950)

2014 Volume 193, Issue 11, Page(s) 5381–5385

Abstract: Candida albicans is the leading cause of systemic candidiasis, a fungal disease associated with high mortality and poor treatment options. The kidney is the target organ during infection and whose control is largely dependent on innate immunity, because ... ...

Abstract	Candida albicans is the leading cause of systemic candidiasis, a fungal disease associated with high mortality and poor treatment options. The kidney is the target organ during infection and whose control is largely dependent on innate immunity, because lymphocytes appear redundant for protection. In this article, we show that this apparent redundancy stems from a failure of Ag-specific CD4(+) T cells to migrate into infected kidneys. In contrast, Ag-specific CD8(+) T cells are recruited normally. Using Ag-loaded immunoliposomes to artificially reverse this defective migration, we show that recruited Ag-specific CD4(+) T cells polarize toward a Th17 phenotype in the kidney and are protective during fungal infection. Therefore, our data explain the redundancy of CD4(+) T cells for defense against systemic infection with C. albicans and have important implications for our understanding of antifungal immunity and the control of renal infections.
MeSH term(s)	Animals ; Antigens/immunology ; Antigens/metabolism ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/microbiology ; CD4-Positive T-Lymphocytes/transplantation ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/microbiology ; Candida albicans/immunology ; Candidiasis/immunology ; Cell Movement ; Cells, Cultured ; Cytoprotection ; Female ; Immunity, Innate ; Kidney/immunology ; Kidney/microbiology ; Liposomes/immunology ; Liposomes/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Receptors, Antigen, T-Cell/genetics ; Th17 Cells/immunology ; Th17 Cells/microbiology
Chemical Substances	Antigens ; Liposomes ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2014-10-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1401675
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