Non-canonical NLRP3 inflammasome activation and IL-1β signaling are necessary to L. amazonensis control mediated by P2X7 receptor and leukotriene B4.
Animals
Inflammasomes
/ genetics
Interleukin-1beta
/ genetics
Leishmania
/ immunology
Leishmaniasis
/ genetics
Leukotriene B4
/ genetics
Macrophages
/ immunology
Mice
Mice, Knockout
NLR Family, Pyrin Domain-Containing 3 Protein
/ genetics
Receptors, Purinergic P2X7
/ genetics
Signal Transduction
/ genetics
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
13
07
2018
accepted:
03
06
2019
revised:
11
07
2019
pubmed:
25
6
2019
medline:
4
12
2019
entrez:
25
6
2019
Statut:
epublish
Résumé
Leishmaniasis is a neglected tropical disease affecting millions of individuals worldwide. P2X7 receptor has been linked to the elimination of Leishmania amazonensis. Biological responses evoked by P2X7 receptor activation have been well-documented, including apoptosis, phagocytosis, cytokine release, such as IL-1β. It was demonstrated that NLRP3 inflammasome activation and IL-1β signaling participated in resistance against L. amazonensis. Furthermore, our group has shown that L. amazonensis elimination through P2X7 receptor activation depended on leukotriene B4 (LTB4) production and release. Therefore, we investigated whether L. amazonensis elimination by P2X7 receptor and LTB4 involved NLRP3 inflammasome activation and IL-1β signaling. We showed that macrophages from NLRP3-/-, ASC-/-, Casp-1/11-/-, gp91phox-/- , and IL-1R-/- mice treated with ATP or LTB4 did not decrease parasitic load as was observed in WT mice. When ASC-/- macrophages were treated with exogenous IL-1β, parasite killing was noted, however, we did not see parasitic load reduction in IL-1R-/- macrophages. Similarly, macrophages from P2X7 receptor-deficient mice treated with IL-1β also showed decreased parasitic load. In addition, when we infected Casp-11-/- macrophages, neither ATP nor LTB4 were able to reduce parasitic load, and Casp-11-/- mice were more susceptible to L. amazonensis infection than were WT mice. Furthermore, P2X7-/- L. amazonensis-infected mice locally treated with exogenous LTB4 showed resistance to infection, characterized by lower parasite load and smaller lesions compared to untreated P2X7-/- mice. A similar observation was noted when infected P2X7-/- mice were treated with IL-1β, i.e., lower parasite load and smaller lesions compared to P2X7-/- mice. These data suggested that L. amazonensis elimination mediated by P2X7 receptor and LTB4 was dependent on non-canonical NLRP3 inflammasome activation, ROS production, and IL-1β signaling.
Identifiants
pubmed: 31233552
doi: 10.1371/journal.ppat.1007887
pii: PPATHOGENS-D-18-01399
pmc: PMC6622556
doi:
Substances chimiques
IL1B protein, mouse
0
Inflammasomes
0
Interleukin-1beta
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
Nlrp3 protein, mouse
0
P2rx7 protein, mouse
0
Receptors, Purinergic P2X7
0
Leukotriene B4
1HGW4DR56D
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1007887Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Cell Mol Life Sci. 2007 Jun;64(12):1471-83
pubmed: 17375261
Am J Physiol Cell Physiol. 2004 May;286(5):C1100-8
pubmed: 15075209
J Immunol. 2006 Sep 1;177(5):3201-8
pubmed: 16920959
J Immunol. 2017 Sep 15;199(6):2055-2068
pubmed: 28784846
Nat Med. 2013 Jul;19(7):909-15
pubmed: 23749230
J Biol Chem. 2004 Sep 24;279(39):40385-91
pubmed: 15252038
Proc Natl Acad Sci U S A. 2014 Apr 22;111(16):6046-51
pubmed: 24715728
Cell Host Microbe. 2014 Aug 13;16(2):249-256
pubmed: 25121752
J Biol Chem. 2012 Oct 5;287(41):34474-83
pubmed: 22898816
PLoS Negl Trop Dis. 2015 Jun 26;9(6):e0003868
pubmed: 26114647
J Immunol. 2016 Feb 15;196(4):1865-73
pubmed: 26800873
Front Cell Infect Microbiol. 2012 Sep 19;2:121
pubmed: 23050244
Int Rev Immunol. 2011 Feb;30(1):16-34
pubmed: 21235323
Immunol Rev. 2011 Sep;243(1):136-51
pubmed: 21884173
J Immunol. 2005 Dec 1;175(11):7611-22
pubmed: 16301671
Purinergic Signal. 2017 Jun;13(2):143-152
pubmed: 27866341
PLoS One. 2015 Jun 08;10(6):e0129048
pubmed: 26053862
Nature. 2010 Oct 14;467(7317):863-7
pubmed: 20944749
Infect Immun. 2002 Aug;70(8):4247-53
pubmed: 12117933
Biochem Soc Trans. 2007 Nov;35(Pt 5):1168-70
pubmed: 17956304
Arthritis Rheum. 2012 Feb;64(2):474-84
pubmed: 21952942
J Immunol. 2006 Feb 15;176(4):2555-61
pubmed: 16456017
J Clin Invest. 2015 Mar 2;125(3):1329-38
pubmed: 25689249
J Biol Chem. 2008 Mar 21;283(12):7657-65
pubmed: 18211888
Immunol Lett. 2019 Jan;205:16-24
pubmed: 30439478
Cell Microbiol. 2011 Sep;13(9):1410-28
pubmed: 21740498
Annu Rev Immunol. 2009;27:229-65
pubmed: 19302040
Science. 2013 Feb 22;339(6122):975-8
pubmed: 23348507
Front Immunol. 2018 Jul 09;9:1531
pubmed: 30038612
Cell Death Differ. 2016 Jul;23(7):1219-31
pubmed: 26868913
PLoS One. 2014 Jan 21;9(1):e85083
pubmed: 24465479
Microbes Infect. 2010 Jun;12(6):497-504
pubmed: 20298798
J Immunol. 2014 May 15;192(10):4765-73
pubmed: 24729618
Parasite Immunol. 1985 Sep;7(5):545-55
pubmed: 3877902
Immunity. 2003 Sep;19(3):403-12
pubmed: 14499115
Front Immunol. 2013 Dec 09;4:440
pubmed: 24367371
Nature. 2006 Mar 9;440(7081):228-32
pubmed: 16407890
PLoS Negl Trop Dis. 2013 Oct 03;7(10):e2469
pubmed: 24098823
PLoS Pathog. 2014 Sep 25;10(9):e1004410
pubmed: 25254654
Free Radic Biol Med. 2007 May 15;42(10):1506-16
pubmed: 17448897
Front Microbiol. 2015 Sep 03;6:913
pubmed: 26388856
mBio. 2014 Feb 18;5(1):
pubmed: 24549849
J Immunol. 2007 Sep 15;179(6):3707-14
pubmed: 17785807
Nature. 2014 May 15;509(7500):366-70
pubmed: 24739961
J Immunol. 2010 Jun 15;184(12):7040-6
pubmed: 20488797
J Immunol. 1996 Dec 15;157(12):5221-4
pubmed: 8955165
J Immunol. 2013 Sep 15;191(6):3373-83
pubmed: 23966627
Biochim Biophys Acta. 2012 Feb;1821(2):249-56
pubmed: 22155285
Eur J Immunol. 2016 Apr;46(4):897-911
pubmed: 26689285
Immunity. 2015 Nov 17;43(5):923-32
pubmed: 26572062
J Clin Invest. 1990 Jun;85(6):1914-24
pubmed: 2112157
Comp Immunol Microbiol Infect Dis. 2004 Sep;27(5):305-18
pubmed: 15225981
Front Immunol. 2017 Oct 12;8:1257
pubmed: 29075257
J Immunol. 2001 Sep 15;167(6):3300-7
pubmed: 11544318
FASEB J. 2017 Nov;31(11):5087-5101
pubmed: 28765172
Free Radic Res. 2010 Jul;44(7):742-50
pubmed: 20370567
J Immunol. 1990 Dec 15;145(12):4284-9
pubmed: 2147940
PLoS One. 2012;7(5):e35671
pubmed: 22693548
Science. 1983 May 6;220(4597):568-75
pubmed: 6301011
Infect Immun. 2015 May;83(5):1940-8
pubmed: 25712931
Infect Immun. 2000 Nov;68(11):6355-61
pubmed: 11035745
Microbes Infect. 2009 Sep;11(10-11):842-9
pubmed: 19439191
Mol Cell. 2002 Aug;10(2):417-26
pubmed: 12191486
Nature. 2011 Oct 16;479(7371):117-21
pubmed: 22002608
Parasit Vectors. 2016 Sep 05;9(1):489
pubmed: 27595742
Cell Rep. 2019 Jan 8;26(2):429-437.e5
pubmed: 30625325
Cell Immunol. 2006 Nov;244(1):10-8
pubmed: 17433275
Lancet. 2005 Oct 29-Nov 4;366(9496):1561-77
pubmed: 16257344