Aberrant type 1 immunity drives susceptibility to mucosal fungal infections

被引：104

作者：

Break, Timothy J. ^{[1
]}

Oikonomou, Vasileios ^{[1
]}

Dutzan, Nicolas ^{[2
]}

Desai, Jigar, V ^{[1
]}

Swidergall, Marc ^{[3
,4
]}

Freiwald, Tilo ^{[5
]}

Chauss, Daniel ^{[5
]}

Harrison, Oliver J. ^{[6
,21
]}

Alejo, Julie ^{[7
]}

Williams, Drake W. ^{[2
]}

Pittaluga, Stefania ^{[7
]}

Lee, Chyi-Chia R. ^{[7
]}

Bouladoux, Nicolas ^{[6
]}

Swamydas, Muthulekha ^{[1
]}

Hoffman, Kevin W. ^{[8
]}

Greenwell-Wild, Teresa ^{[2
]}

Bruno, Vincent M. ^{[9
]}

Rosen, Lindsey B. ^{[10
]}

Lwin, Wint ^{[11
]}

Renteria, Andy ^{[1
]}

Pontejo, Sergio M. ^{[12
]}

Shannon, John P. ^{[13
]}

Myles, Ian A. ^{[14
]}

Olbrich, Peter ^{[10
]}

Ferre, Elise M. N. ^{[1
]}

Schmitt, Monica ^{[1
]}

Martin, Daniel ^{[15
]}

Barber, Daniel L. ^{[17
]}

Solis, Norma, V ^{[3
]}

Notarangelo, Luigi D. ^{[18
]}

Serreze, David, V ^{[19
]}

Matsumoto, Mitsuru ^{[20
]}

Hickman, Heather D. ^{[13
]}

Murphy, Philip M. ^{[12
]}

Anderson, Mark S. ^{[1
]}

Lim, Jean K. ^{[8
]}

Holland, Steven M. ^{[10
]}

Filler, Scott G. ^{[3
,4
]}

Afzali, Behdad ^{[5
]}

Belkaid, Yasmine ^{[6
]}

Moutsopoulos, Niki M. ^{[2
]}

Lionakis, Michail S. ^{[1
]}

机构：

[1] NIAID, Fungal Pathogenesis Sect, Lab Clin Immunol & Microbiol LCIM, 9000 Rockville Pike, Bethesda, MD 20892 USA

[2] Natl Inst Dent & Craniofacial Res NIDCR, Oral Immun & Inflammat Sect, Bethesda, MD USA

[3] Harbor UCLA Med Ctr, Lundquist Inst Biomed Innovat, Torrance, CA 90509 USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA

[5] NIDDK, Immunoregulat Sect, Kidney Dis Branch, Bethesda, MD USA

[6] NIAID, Metaorganism Immun Sect, Lab Immune Syst Biol, 9000 Rockville Pike, Bethesda, MD 20892 USA

[7] NCI, Lab Pathol, Ctr Canc Res, Bethesda, MD 20892 USA

[8] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA

[9] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA

[10] NIAID, Immunopathogenesis Sect, LCIM, 9000 Rockville Pike, Bethesda, MD 20892 USA

[11] Univ Calif San Francisco, Diabet Ctr, San Francisco, CA 94143 USA

[12] NIAID, Mol Signaling Sect, Lab Mol Immunol, 9000 Rockville Pike, Bethesda, MD 20892 USA

[13] NIAID, Viral Immun & Pathogenesis Unit, LCIM, 9000 Rockville Pike, Bethesda, MD 20892 USA

[14] NIAID, Epithelial Therapeut Unit, LCIM, 9000 Rockville Pike, Bethesda, MD 20892 USA

[15] NIDCR, Genom & Computat Biol Core, Bethesda, MD USA

[16] Natl Inst Deafness & Other Commun Disorders NIDCD, Genom & Computat Biol Core, Bethesda, MD USA

[17] NIAID, T Lymphocyte Biol Sect, Lab Parasit Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA

[18] NIAID, Immune Deficiency Genet Sect, LCIM, 9000 Rockville Pike, Bethesda, MD 20892 USA

[19] Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA

[20] Tokushima Univ, Inst Enzyme Res, Div Mol Immunol, Tokushima, Japan

[21] Benaroya Res Inst Virginia Mason, 1201 Ninth Avenge, Seattle, WA 98101 USA

来源：

SCIENCE | 2021年 / 371卷 / 6526期

关键词：

CHRONIC MUCOCUTANEOUS CANDIDIASIS; STAT1; MUTATIONS; AIRE; CELLS; MICE; BACTERIAL; MODEL; AUTOIMMUNITY; RUXOLITINIB; MECHANISMS;

D O I：

10.1126/science.aay5731

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Human monogenic disorders have revealed the critical contribution of type 17 responses in mucosal fungal surveillance. We unexpectedly found that in certain settings, enhanced type 1 immunity rather than defective type 17 responses can promote mucosal fungal infection susceptibility. Notably, in mice and humans with AIRE deficiency, an autoimmune disease characterized by selective susceptibility to mucosal but not systemic fungal infection, mucosal type 17 responses are intact while type 1 responses are exacerbated. These responses promote aberrant interferon-gamma (IFN-gamma)- and signal transducer and activator of transcription 1 (STAT1)-dependent epithelial barrier defects as well as mucosal fungal infection susceptibility. Concordantly, genetic and pharmacologic inhibition of IFN-gamma or Janus kinase (JAK)-STAT signaling ameliorates mucosal fungal disease. Thus, we identify aberrant T cell-dependent, type 1 mucosal inflammation as a critical tissue-specific pathogenic mechanism that promotes mucosal fungal infection susceptibility in mice and humans.

引用

页码：252 / +

页数：76

共 74 条

[1] Optimization of the ligature-induced periodontitis model in mice
Abe, Toshiharu
Hajishengallis, George
[J]. JOURNAL OF IMMUNOLOGICAL METHODS, 2013, 394 (1-2) : 49 - 54
[2] Oral epithelial IL-22/STAT3 signaling licenses IL-17-mediated immunity to oral mucosal candidiasis
Aggor, Felix E. Y.
Break, Timothy J.
Trevejo-Nunez, Giraldina
Whibley, Natasha
Coleman, Bianca M.
Bailey, Rachel D.
Kaplan, Daniel H.
Naglik, Julian R.
Shan, Wei
Shetty, Amol C.
McCracken, Carrie
Durum, Scott K.
Biswas, Partha S.
Bruno, Vincent M.
Kolls, Jay K.
Lionakis, Michail S.
Gaffen, Sarah L.
[J]. SCIENCE IMMUNOLOGY, 2020, 5 (48)
[3] Emapalumab: First Global Approval
Al-Salama, Zaina T.
[J]. DRUGS, 2019, 79 (01) : 99 - 103
[4] Projection of an immunological self shadow within the thymus by the aire protein
Anderson, MS
Venanzi, ES
Klein, L
Chen, ZB
Berzins, SP
Turley, SJ
von Boehmer, H
Bronson, R
Dierich, A
Benoist, C
Mathis, D
[J]. SCIENCE, 2002, 298 (5597) : 1395 - 1401
[5] Multi-omits: Differential expression of IFN-γ results in distinctive mechanistic features linking chronic inflammation, gut dysbiosis, and autoimmune diseases
Bae, Heekyong R.
Leung, Patrick S. C.
Hodge, Deborah L.
Fenimore, John M.
Jeon, Seon-Min
Thovarai, Vishal
Dzutsev, Amiran
Welcher, Andrew A.
Boedigheimer, Michael
Damore, Michael A.
Choi, Myung-Sook
Fravell, Richard A.
Trinchieri, Giorgio
Gershwin, M. Eric
Young, Howard A.
[J]. JOURNAL OF AUTOIMMUNITY, 2020, 111
[6] An ACT1 Mutation Selectively Abolishes Interleukin-17 Responses in Humans with Chronic Mucocutaneous Candidiasis
Boisson, Bertrand
Wang, Chenhui
Pedergnana, Vincent
Wu, Ling
Cypowyj, Sophie
Rybojad, Michel
Belkadi, Aziz
Picard, Capucine
Abel, Laurent
Fieschi, Claire
Puel, Anne
Li, Xiaoxia
Casanova, Jean-Laurent
[J]. IMMUNITY, 2013, 39 (04) : 676 - 686
[7] Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2
Bolyen, Evan
Rideout, Jai Ram
Dillon, Matthew R.
Bokulich, NicholasA.
Abnet, Christian C.
Al-Ghalith, Gabriel A.
Alexander, Harriet
Alm, Eric J.
Arumugam, Manimozhiyan
Asnicar, Francesco
Bai, Yang
Bisanz, Jordan E.
Bittinger, Kyle
Brejnrod, Asker
Brislawn, Colin J.
Brown, C. Titus
Callahan, Benjamin J.
Caraballo-Rodriguez, Andres Mauricio
Chase, John
Cope, Emily K.
Da Silva, Ricardo
Diener, Christian
Dorrestein, Pieter C.
Douglas, Gavin M.
Durall, Daniel M.
Duvallet, Claire
Edwardson, Christian F.
Ernst, Madeleine
Estaki, Mehrbod
Fouquier, Jennifer
Gauglitz, Julia M.
Gibbons, Sean M.
Gibson, Deanna L.
Gonzalez, Antonio
Gorlick, Kestrel
Guo, Jiarong
Hillmann, Benjamin
Holmes, Susan
Holste, Hannes
Huttenhower, Curtis
Huttley, Gavin A.
Janssen, Stefan
Jarmusch, Alan K.
Jiang, Lingjing
Kaehler, Benjamin D.
Bin Kang, Kyo
Keefe, Christopher R.
Keim, Paul
Kelley, Scott T.
Knights, Dan
[J]. NATURE BIOTECHNOLOGY, 2019, 37 (08) : 852 - 857
[8] Bouladoux Nicolas, 2017, Curr Protoc Immunol, V119, DOI 10.1002/cpim.34
[9] VT-1598 inhibits the in vitro growth of mucosal Candida strains and protects against fluconazole-susceptible and -resistant oral candidiasis in IL-17 signalling-deficient mice
Break, Timothy J.
Desai, Jigar V.
Healey, Kelley R.
Natarajan, Mukil
Ferre, Elise M. N.
Henderson, Christina
Zelazny, Adrian
Siebenlist, Ulrich
Yates, Christopher M.
Cohen, Oren J.
Schotzinger, Robert J.
Perlin, David S.
Garvey, Edward P.
Lionakis, Michail S.
[J]. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2018, 73 (08) : 2089 - 2094
[10] VT-1161 protects mice against oropharyngeal candidiasis caused by fluconazole-susceptible and -resistant Candida albicans
Break, Timothy J.
Desai, Jigar V.
Natarajan, Mukil
Ferre, Elise M. N.
Henderson, Christina
Zelazny, Adrian M.
Siebenlist, Ulrich
Hoekstra, William J.
Schotzinger, Robert J.
Garvey, Edward P.
Lionakis, Michail S.
[J]. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2018, 73 (01) : 151 - 155

← 1 2 3 4 5 6 7 8 →