TLR2 and endosomal TLR-mediated secretion of IL-10 and immune suppression in response to phagosome-confined Listeria monocytogenes.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
08
01
2020
accepted:
12
05
2020
entrez:
8
7
2020
pubmed:
8
7
2020
medline:
21
8
2020
Statut:
epublish
Résumé
Listeria monocytogenes is a facultative intracellular bacterial pathogen that escapes from phagosomes and induces a robust adaptive immune response in mice, while mutants unable to escape phagosomes fail to induce a robust adaptive immune response and suppress the immunity to wildtype bacteria when co-administered. The capacity to suppress immunity can be reversed by blocking IL-10. In this study, we sought to understand the host receptors that lead to secretion of IL-10 in response to phagosome-confined L. monocytogenes (Δhly), with the ultimate goal of generating strains that fail to induce IL-10. We conducted a transposon screen to identify Δhly L. monocytogenes mutants that induced significantly more or less IL-10 secretion in bone marrow-derived macrophages (BMMs). A transposon insertion in lgt, which encodes phosphatidylglycerol-prolipoprotein diacylglyceryl transferase and is essential for the formation of lipoproteins, induced significantly reduced IL-10 secretion. Mutants with transposon insertions in pgdA and oatA, which encode peptidoglycan N-acetylglucosamine deacetylase and O-acetyltransferase, are sensitive to lysozyme and induced enhanced IL-10 secretion. A ΔhlyΔpgdAΔoatA strain was killed in BMMs and induced enhanced IL-10 secretion that was dependent on Unc93b1, a trafficking molecule required for signaling of nucleic acid-sensing TLRs. These data revealed that nucleic acids released by bacteriolysis triggered endosomal TLR-mediated IL-10 secretion. Secretion of IL-10 in response to infection with the parental strain was mostly TLR2-dependent, while IL-10 secretion in response to lysozyme-sensitive strains was dependent on TLR2 and Unc93b1. In mice, the IL-10 response to vacuole-confined L. monocytogenes was also dependent on TLR2 and Unc93b1. Co-administration of Δhly and ΔactA resulted in suppressed immunity in WT mice, but not in mice with mutations in Unc93b1. These data revealed that secretion of IL-10 in response to L. monocytogenes infection in vitro is mostly TLR2-dependent and immune suppression by phagosome-confined bacteria in vivo is mostly dependent on endosomal TLRs.
Identifiants
pubmed: 32634175
doi: 10.1371/journal.ppat.1008622
pii: PPATHOGENS-D-20-00037
pmc: PMC7340287
doi:
Substances chimiques
IL10 protein, mouse
0
Tlr2 protein, mouse
0
Toll-Like Receptor 2
0
Toll-Like Receptors
0
Interleukin-10
130068-27-8
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008622Subventions
Organisme : NIAID NIH HHS
ID : P01 AI063302
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI027655
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
J Exp Med. 1988 Apr 1;167(4):1459-71
pubmed: 2833557
Int J Biochem Cell Biol. 2008;40(4):586-91
pubmed: 17468031
Immunology. 1990 Sep;71(1):107-12
pubmed: 2120126
PLoS One. 2013 Dec 12;8(12):e80743
pubmed: 24349012
Nat Commun. 2016 Jan 05;7:10198
pubmed: 26729647
Nat Rev Immunol. 2004 Oct;4(10):812-23
pubmed: 15459672
J Bacteriol. 2016 Jun 13;198(13):1847-56
pubmed: 27114466
Microbiol Mol Biol Rev. 2007 Jun;71(2):377-97
pubmed: 17554049
Adv Exp Med Biol. 2013;785:1-8
pubmed: 23456832
J Biol Chem. 2015 Feb 6;290(6):3209-22
pubmed: 25505250
Nat Rev Immunol. 2010 Mar;10(3):170-81
pubmed: 20154735
Infect Immun. 1994 Dec;62(12):5608-13
pubmed: 7960143
Immunity. 2005 Apr;22(4):507-17
pubmed: 15845454
Sci Immunol. 2017 Oct 6;2(16):
pubmed: 28986418
J Biol Chem. 1994 Aug 5;269(31):19701-6
pubmed: 8051048
Infect Immun. 2011 Feb;79(2):548-61
pubmed: 20974828
J Bacteriol. 2009 Jun;191(12):3950-64
pubmed: 19376879
Front Immunol. 2020 Feb 21;11:269
pubmed: 32153579
J Immunol. 2008 May 1;180(9):5771-7
pubmed: 18424693
J Bacteriol. 2014 Nov;196(21):3756-67
pubmed: 25157076
Nature. 1999 Oct 21;401(6755):811-5
pubmed: 10548109
J Exp Med. 2003 Jan 6;197(1):7-17
pubmed: 12515809
Infect Immun. 2011 Sep;79(9):3596-606
pubmed: 21768286
Mol Microbiol. 1993 Apr;8(1):143-57
pubmed: 8388529
PLoS Pathog. 2007 Mar;3(3):e51
pubmed: 17397264
PLoS Pathog. 2011 Mar;7(3):e1001326
pubmed: 21455492
J Immunol. 2006 Dec 1;177(11):7551-8
pubmed: 17114424
Nat Rev Immunol. 2013 Jun;13(6):453-60
pubmed: 23681101
PLoS Pathog. 2009 Sep;5(9):e1000568
pubmed: 19730694
J Bacteriol. 2007 Jan;189(2):313-24
pubmed: 17041050
Nature. 2008 Mar 13;452(7184):234-8
pubmed: 18305481
Trends Immunol. 2012 Oct;33(10):488-95
pubmed: 22677184
J Immunol. 1987 Apr 1;138(7):2266-71
pubmed: 3104455
J Immunol. 2008 Aug 1;181(3):2028-35
pubmed: 18641340
J Immunol. 2004 Sep 1;173(5):3392-7
pubmed: 15322203
Nat Immunol. 2006 Feb;7(2):156-64
pubmed: 16415873
Curr Opin Pharmacol. 2018 Aug;41:128-136
pubmed: 29890457
Cell Host Microbe. 2009 Jul 23;6(1):10-21
pubmed: 19616762
PLoS Pathog. 2016 Jun 13;12(6):e1005708
pubmed: 27295349
Infect Immun. 2006 Nov;74(11):6387-97
pubmed: 16954391
Adv Immunol. 2012;113:135-56
pubmed: 22244582
Elife. 2013 Feb 19;2:e00291
pubmed: 23426999
PLoS One. 2010 Sep 22;5(9):e12871
pubmed: 20877569
Immunity. 2009 Dec 18;31(6):847-9
pubmed: 20064441
Int Immunol. 2014 Oct;26(10):563-73
pubmed: 24860120
Microbes Infect. 2007 Aug;9(10):1208-15
pubmed: 17719259
Cell Rep. 2018 May 29;23(9):2582-2594
pubmed: 29847790
J Exp Med. 1989 Dec 1;170(6):2141-6
pubmed: 2511268
Dev Comp Immunol. 2014 May;44(1):44-9
pubmed: 24291017
Nat Commun. 2017 Dec 21;8(1):2246
pubmed: 29269769
J Immunol. 2006 Aug 15;177(4):2565-74
pubmed: 16888018
J Immunol. 1997 Mar 1;158(5):2259-67
pubmed: 9036973
J Bacteriol. 2002 Aug;184(15):4177-86
pubmed: 12107135
Mol Microbiol. 2000 Jan;35(2):312-23
pubmed: 10652092
J Biol Chem. 2012 Apr 13;287(16):13170-81
pubmed: 22303020
Microbes Infect. 2011 Apr;13(4):350-8
pubmed: 21172450
Nature. 1970 Nov 28;228(5274):855-6
pubmed: 5477011