Transcriptional and functional insights into the host immune response against the emerging fungal pathogenCandida auris

被引：81

作者：

Bruno, Mariolina ^{[1
]}

Kersten, Simone ^{[1
,2
]}

Bain, Judith M. ^{[3
]}

Jaeger, Martin ^{[1
]}

Rosati, Diletta ^{[1
]}

Kruppa, Michael D. ^{[4
,5
,6
]}

Lowman, Douglas W. ^{[4
,5
,6
]}

Rice, Peter J. ^{[7
]}

Graves, Bridget ^{[4
,5
,6
]}

Ma, Zuchao ^{[4
,5
,6
]}

Jiao, Yue Ning ^{[4
,5
,6
]}

Chowdhary, Anuradha ^{[8
]}

Renieris, George ^{[9
]}

van de Veerdonk, Frank L. ^{[1
,10
,11
]}

Kullberg, Bart-Jan ^{[1
,10
,11
]}

Giamarellos-Bourboulis, Evangelos J. ^{[9
]}

Hoischen, Alexander ^{[1
,2
]}

Gow, Neil A. R. ^{[3
,12
]}

Brown, Alistair J. P. ^{[3
,12
]}

Meis, Jacques F. ^{[10
,11
,13
,14
]}

Williams, David L. ^{[4
,5
,6
]}

Netea, Mihai G. ^{[1
,15
]}

机构：

[1] Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Dept Internal Med, Med Ctr, Nijmegen, Netherlands

[2] Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Dept Human Genet, Med Ctr, Nijmegen, Netherlands

[3] Univ Aberdeen, Ctr Med Mycol, MRC, Aberdeen, Scotland

[4] East Tennessee State Univ, Quillen Coll Med, Dept Surg, Johnson City, TN USA

[5] East Tennessee State Univ, Quillen Coll Med, Dept Biomed Sci, Johnson City, TN USA

[6] East Tennessee State Univ, Quillen Coll Med, Ctr Excellence Inflammat Infect Dis & Immun, Johnson City, TN USA

[7] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Dept Clin Pharm, Aurora, CO USA

[8] Univ Delhi, Vallabhbhai Patel Chest Inst, Dept Med Mycol, New Delhi, India

[9] Natl & Kapodistrian Univ Athens, Med Sch, Dept Internal Med 4, Athens, Greece

[10] Radboud Univ Nijmegen, Med Ctr, Ctr Expertise Mycol, Nijmegen, Netherlands

[11] Canisius Wilhelmina Hosp, Nijmegen, Netherlands

[12] Univ Exeter, Ctr Med Mycol, MRC, Exeter, Devon, England

[13] Univ Fed Parana, Bioproc Engn & Biotechnol Grad Program, Curitiba, Parana, Brazil

[14] Canisius Wilhelmina Hosp, Dept Med Microbiol & Infect Dis, Nijmegen, Netherlands

[15] Univ Bonn, Life & Med Sci Inst LIMES, Dept Genom & Immunoregulat, Bonn, Germany

来源：

NATURE MICROBIOLOGY | 2020年 / 5卷 / 12期

基金：

英国医学研究理事会; 美国国家卫生研究院;

关键词：

RESISTANT CANDIDA-AURIS; ALBICANS; RECOGNITION; MANNAN; YEAST; EMERGENCE; SURVIVAL; LECTIN; GLUCAN; BLOOD;

D O I：

10.1038/s41564-020-0780-3

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Transcriptional and functional immune-cell profiling reveals thatCandida aurisis a strong inducer of innate host defence and identifies possible targets for adjuvant immunotherapy. Candida aurisis among the most important emerging fungal pathogens, yet mechanistic insights into its immune recognition and control are lacking. Here, we integrate transcriptional and functional immune-cell profiling to uncover innate defence mechanisms againstC. auris.C. aurisinduces a specific transcriptome in human mononuclear cells, a stronger cytokine response compared withCandida albicans, but a lower macrophage lysis capacity.C. auris-induced innate immune activation is mediated through the recognition of C-type lectin receptors, mainly elicited by structurally uniqueC. aurismannoproteins. In in vivo experimental models of disseminated candidiasis,C. auriswas less virulent thanC. albicans. Collectively, these results demonstrate thatC. aurisis a strong inducer of innate host defence, and identify possible targets for adjuvant immunotherapy.

引用

页码：1516 / +

页数：33

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