Asthma-protective agents in dust from traditional farm environments.
Asthma
asthma protection
farm effect
microbial metabolites
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
12
12
2022
revised:
05
04
2023
accepted:
05
05
2023
pmc-release:
01
09
2024
medline:
11
9
2023
pubmed:
5
6
2023
entrez:
4
6
2023
Statut:
ppublish
Résumé
Growing up on traditional European or US Amish dairy farms in close contact with cows and hay protects children against asthma, and airway administration of extracts from dust collected from cowsheds of those farms prevents allergic asthma in mice. This study sought to begin identifying farm-derived asthma-protective agents. Our work unfolded along 2 unbiased and independent but complementary discovery paths. Dust extracts (DEs) from protective and nonprotective farms (European and Amish cowsheds vs European sheep sheds) were analyzed by comparative nuclear magnetic resonance profiling and differential proteomics. Bioactivity-guided size fractionation focused on protective Amish cowshed DEs. Multiple in vitro and in vivo functional assays were used in both paths. Some of the proteins thus identified were characterized by in-solution and in-gel sodium dodecyl sulfate-polyacrylamide gel electrophoresis enzymatic digestion/peptide mapping followed by liquid chromatography/mass spectrometry. The cargo carried by these proteins was analyzed by untargeted liquid chromatography-high-resolution mass spectrometry. Twelve carrier proteins of animal and plant origin, including the bovine lipocalins Bos d 2 and odorant binding protein, were enriched in DEs from protective European cowsheds. A potent asthma-protective fraction of Amish cowshed DEs (≈0.5% of the total carbon content of unfractionated extracts) contained 7 animal and plant proteins, including Bos d 2 and odorant binding protein loaded with fatty acid metabolites from plants, bacteria, and fungi. Animals and plants from traditional farms produce proteins that transport hydrophobic microbial and plant metabolites. When delivered to mucosal surfaces, these agents might regulate airway responses.
Sections du résumé
BACKGROUND
Growing up on traditional European or US Amish dairy farms in close contact with cows and hay protects children against asthma, and airway administration of extracts from dust collected from cowsheds of those farms prevents allergic asthma in mice.
OBJECTIVES
This study sought to begin identifying farm-derived asthma-protective agents.
METHODS
Our work unfolded along 2 unbiased and independent but complementary discovery paths. Dust extracts (DEs) from protective and nonprotective farms (European and Amish cowsheds vs European sheep sheds) were analyzed by comparative nuclear magnetic resonance profiling and differential proteomics. Bioactivity-guided size fractionation focused on protective Amish cowshed DEs. Multiple in vitro and in vivo functional assays were used in both paths. Some of the proteins thus identified were characterized by in-solution and in-gel sodium dodecyl sulfate-polyacrylamide gel electrophoresis enzymatic digestion/peptide mapping followed by liquid chromatography/mass spectrometry. The cargo carried by these proteins was analyzed by untargeted liquid chromatography-high-resolution mass spectrometry.
RESULTS
Twelve carrier proteins of animal and plant origin, including the bovine lipocalins Bos d 2 and odorant binding protein, were enriched in DEs from protective European cowsheds. A potent asthma-protective fraction of Amish cowshed DEs (≈0.5% of the total carbon content of unfractionated extracts) contained 7 animal and plant proteins, including Bos d 2 and odorant binding protein loaded with fatty acid metabolites from plants, bacteria, and fungi.
CONCLUSIONS
Animals and plants from traditional farms produce proteins that transport hydrophobic microbial and plant metabolites. When delivered to mucosal surfaces, these agents might regulate airway responses.
Identifiants
pubmed: 37271318
pii: S0091-6749(23)00706-6
doi: 10.1016/j.jaci.2023.05.013
pmc: PMC10680491
mid: NIHMS1914639
pii:
doi:
Substances chimiques
Dust
0
Allergens
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
610-621Subventions
Organisme : NIAID NIH HHS
ID : P01 AI148104
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI144722
Pays : United States
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Références
Curr Opin Allergy Clin Immunol. 2003 Oct;3(5):343-6
pubmed: 14501432
J Biomol NMR. 2013 Nov;57(3):313-8
pubmed: 24057444
J Agric Food Chem. 2011 May 25;59(10):5729-37
pubmed: 21506515
Biochim Biophys Acta. 2003 May 30;1648(1-2):99-104
pubmed: 12758152
N Engl J Med. 2016 Aug 4;375(5):411-421
pubmed: 27518660
BMC Struct Biol. 2016 Jun 01;16(1):8
pubmed: 27251136
Chemosphere. 1997 Jul;35(1-2):275-94
pubmed: 9232001
Science. 2015 Sep 4;349(6252):1106-10
pubmed: 26339029
Am J Respir Crit Care Med. 1997 Feb;155(2):661-9
pubmed: 9032210
J Biomol NMR. 1995 Jan;5(1):67-81
pubmed: 7881273
Pediatr Pulmonol. 2002 Oct;34(4):267-77
pubmed: 12205568
Biochim Biophys Acta. 2009 Jun;1790(6):527-37
pubmed: 19362581
J Clin Invest. 1997 Dec 15;100(12):3083-92
pubmed: 9399955
Clin Exp Allergy. 2014 Sep;44(9):1188-99
pubmed: 25039815
Nat Rev Immunol. 2021 Nov;21(11):739-751
pubmed: 33846604
J Allergy Clin Immunol. 2007 May;119(5):1140-7
pubmed: 17349684
J Environ Qual. 2002 Mar-Apr;31(2):375-87
pubmed: 11931424
Sci Rep. 2016 Mar 23;6:23600
pubmed: 27004988
Mol Immunol. 2012 Oct;52(3-4):174-82
pubmed: 22677715
Thorax. 2006 Feb;61(2):134-9
pubmed: 16244088
FASEB J. 2018 Jan;32(1):304-318
pubmed: 28904023
Nat Rev Immunol. 2010 Dec;10(12):861-8
pubmed: 21060319
Allergy. 2022 Oct;77(10):2949-2960
pubmed: 35531632
J Biol Chem. 1955 Mar;213(1):415-23
pubmed: 14353942
J Allergy Clin Immunol. 2021 Jan;147(1):321-334.e4
pubmed: 32485264
Lancet. 2001 Oct 6;358(9288):1129-33
pubmed: 11597666
J Allergy Clin Immunol. 2012 Jun;129(6):1470-7.e6
pubmed: 22534534
World Allergy Organ J. 2013 Jan 31;6(1):3
pubmed: 23663440
J Appl Microbiol. 2015 Nov;119(5):1207-18
pubmed: 26184497
J Allergy Clin Immunol. 2020 Jan;145(1):415-426
pubmed: 31606483
Biochem J. 1996 Aug 15;318 ( Pt 1):1-14
pubmed: 8761444
Clin Transl Allergy. 2022 Feb 12;12(2):e12125
pubmed: 35169442
Clin Exp Allergy. 2003 Feb;33(2):153-5
pubmed: 12580903
J Allergy Clin Immunol. 2010 Sep;126(3):648-56.e1-4
pubmed: 20621350
Acta Crystallogr D Biol Crystallogr. 2001 Jan;57(Pt 1):20-9
pubmed: 11134923
Biochemistry. 2009 Nov 10;48(44):10591-600
pubmed: 19810752
Food Nutr Res. 2008;52:
pubmed: 19109654
Dairy Sci Technol. 2014;94:409-426
pubmed: 25110551
J Allergy Clin Immunol. 2018 May;141(5):1949-1952.e8
pubmed: 29425849
N Engl J Med. 2016 Nov 10;375(19):1898-1899
pubmed: 27959651
J Biosci Bioeng. 2005 Oct;100(4):355-64
pubmed: 16310724
ISME J. 2009 May;3(5):606-17
pubmed: 19194481
Molecules. 2018 Oct 09;23(10):
pubmed: 30304860
Methods Enzymol. 2009;459:395-433
pubmed: 19362649
J Allergy Clin Immunol. 2022 Mar;149(3):943-956
pubmed: 34560105