Aspergillus fumigatus corneal infection is regulated by chitin synthases and by neutrophil-derived acidic mammalian chitinase.
Acidic mammalian chitinase
Aspergillus fumigatus
Chitin synthase
Corneal infection
Keratitis
Neutrophil
Journal
European journal of immunology
ISSN: 1521-4141
Titre abrégé: Eur J Immunol
Pays: Germany
ID NLM: 1273201
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
06
08
2018
revised:
24
01
2019
accepted:
19
03
2019
pubmed:
25
3
2019
medline:
28
5
2020
entrez:
24
3
2019
Statut:
ppublish
Résumé
Aspergillus fumigatus is an important cause of pulmonary and systemic infections in immune compromised individuals, and of corneal ulcers and blindness in immune competent patients. To examine the role of chitin synthases in Aspergillus corneal infection, we analyzed Aspergillus mutants of chitin synthase family 1 and family 2, and found that compared with the parent strain, the quadruple mutants from both families were more readily killed by neutrophils in vitro, and that both also exhibited impaired hyphal growth in the cornea. Further, inhibition of chitin synthases using Nikkomycin Z enhanced neutrophil killing in vitro and in vivo in a murine model of A. fumigatus corneal infection. Acidic mammalian chitinase (AMCase) is mostly produced by macrophages in asthmatic lungs; however, we now demonstrate that neutrophils are a major source of AMCase, which inhibits hyphal growth. In A. fumigatus corneal infection, neutrophils are the major source of AMCase, and addition of AMCase inhibitors or adoptive transfer of neutrophils from AMCase
Identifiants
pubmed: 30903663
doi: 10.1002/eji.201847851
pmc: PMC6999821
mid: NIHMS1064386
doi:
Substances chimiques
Chitin Synthase
EC 2.4.1.16
Chitinases
EC 3.2.1.14
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
918-927Subventions
Organisme : NEI NIH HHS
ID : F32 EY022278
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY011373
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY018612
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI089474
Pays : United States
Informations de copyright
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Références
mBio. 2016 May 31;7(3):
pubmed: 27247234
Annu Rev Microbiol. 2017 Sep 8;71:99-116
pubmed: 28701066
Biochim Biophys Acta. 1966 Jan 11;113(1):51-6
pubmed: 5940632
PLoS Pathog. 2010 Jul 01;6:e1000976
pubmed: 20617171
J Biol Chem. 2002 Jul 12;277(28):25537-44
pubmed: 11960986
Fungal Genet Biol. 2011 Apr;48(4):418-29
pubmed: 21184840
Annu Rev Physiol. 2011;73:479-501
pubmed: 21054166
Eur J Immunol. 2017 Oct;47(10):1584-1797
pubmed: 29023707
J Immunol. 2008 Sep 15;181(6):4279-86
pubmed: 18768886
J Immunol. 2008 Jul 1;181(1):593-600
pubmed: 18566426
Am J Respir Crit Care Med. 2005 Dec 15;172(12):1505-9
pubmed: 16179638
Microbes Infect. 2013 Apr;15(4):259-69
pubmed: 23220005
Cell Microbiol. 2014 Dec;16(12):1784-805
pubmed: 24946720
Microbiol Spectr. 2017 May;5(3):
pubmed: 28513415
Surv Ophthalmol. 2019 May - Jun;64(3):255-271
pubmed: 30590103
Antimicrob Agents Chemother. 2012 Mar;56(3):1595-8
pubmed: 22203603
Nat Rev Microbiol. 2012 Jul 16;10(8):525-37
pubmed: 22796883
J Clin Invest. 2012 Jul;122(7):2482-98
pubmed: 22706306
Sci Transl Med. 2012 Dec 19;4(165):165rv13
pubmed: 23253612
Curr Opin Immunol. 2008 Dec;20(6):684-9
pubmed: 18938241
PLoS Pathog. 2013;9(7):e1003436
pubmed: 23853581
J Fungi (Basel). 2017 Oct 18;3(4):null
pubmed: 29371573
PLoS One. 2015 Oct 30;10(10):e0141730
pubmed: 26517273
Cytokine. 2012 Apr;58(1):107-11
pubmed: 22280957
J Bacteriol. 1994 Sep;176(18):5857-60
pubmed: 8083179
J Biol Chem. 2011 Oct 14;286(41):35447-55
pubmed: 21862582
Science. 2004 Jun 11;304(5677):1678-82
pubmed: 15192232
Int J Microbiol. 2012;2012:920459
pubmed: 22187561
Chem Biol. 2011 May 27;18(5):569-79
pubmed: 21609838
PLoS Pathog. 2014 Apr 10;10(4):e1004050
pubmed: 24722226
Trends Microbiol. 1995 Mar;3(3):98-104
pubmed: 7773595
Cell. 2017 Apr 20;169(3):497-509.e13
pubmed: 28431248
Yeast. 2002 Mar 15;19(4):341-9
pubmed: 11870857
Int Arch Allergy Immunol. 2009;149(4):369-77
pubmed: 19295241
J Immunol. 2016 Jan 1;196(1):336-44
pubmed: 26582948
J Immunol. 2009 Mar 15;182(6):3573-82
pubmed: 19265136
Nat Immunol. 2016 May;17(5):538-44
pubmed: 27043413
Annu Rev Microbiol. 1994;48:471-97
pubmed: 7826015
ACS Med Chem Lett. 2011 Mar 23;2(6):428-32
pubmed: 24900325
Am J Respir Cell Mol Biol. 2012 Jan;46(1):71-9
pubmed: 21836154
J Infect Dis. 2011 Sep 15;204(6):942-50
pubmed: 21828275
Infect Immun. 1997 May;65(5):1734-41
pubmed: 9125555
J Immunol. 2018 Nov 1;201(9):2767-2775
pubmed: 30266768
Trends Pharmacol Sci. 2004 Oct;25(10):509-11
pubmed: 15380933
Infect Immun. 2018 Jun 21;86(7):
pubmed: 29712728
Front Immunol. 2018 May 29;9:1182
pubmed: 29896200
J Immunol. 2013 Sep 1;191(5):2581-8
pubmed: 23926321