Schistosome immunomodulators.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
entrez:
30
12
2021
pubmed:
31
12
2021
medline:
19
2
2022
Statut:
epublish
Résumé
Schistosomes are long lived, intravascular parasitic platyhelminths that infect >200 million people globally. The molecular mechanisms used by these blood flukes to dampen host immune responses are described in this review. Adult worms express a collection of host-interactive tegumental ectoenzymes that can cleave host signaling molecules such as the "alarmin" ATP (cleaved by SmATPDase1), the platelet activator ADP (SmATPDase1, SmNPP5), and can convert AMP into the anti-inflammatory mediator adenosine (SmAP). SmAP can additionally cleave the lipid immunomodulator sphingosine-1-phosphate and the proinflammatory anionic polymer, polyP. In addition, the worms release a barrage of proteins (e.g., SmCB1, SjHSP70, cyclophilin A) that can impinge on immune cell function. Parasite eggs also release their own immunoregulatory proteins (e.g., IPSE/α1, omega1, SmCKBP) as do invasive cercariae (e.g., Sm16, Sj16). Some schistosome glycans (e.g., LNFPIII, LNnT) and lipids (e.g., Lyso-PS, LPC), produced by several life stages, likewise affect immune cell responses. The parasites not only produce eicosanoids (e.g., PGE2, PGD2-that can be anti-inflammatory) but can also induce host cells to release these metabolites. Finally, the worms release extracellular vesicles (EVs) containing microRNAs, and these too have been shown to skew host cell metabolism. Thus, schistosomes employ an array of biomolecules-protein, lipid, glycan, nucleic acid, and more, to bend host biochemistry to their liking. Many of the listed molecules have been individually shown capable of inducing aspects of the polarized Th2 response seen following infection (with the generation of regulatory T cells (Tregs), regulatory B cells (Bregs) and anti-inflammatory, alternatively activated (M2) macrophages). Precisely how host cells integrate the impact of these myriad parasite products following natural infection is not known. Several of the schistosome immunomodulators described here are in development as novel therapeutics against autoimmune, inflammatory, and other, nonparasitic, diseases.
Identifiants
pubmed: 34969052
doi: 10.1371/journal.ppat.1010064
pii: PPATHOGENS-D-21-00850
pmc: PMC8718004
doi:
Substances chimiques
Helminth Proteins
0
Immunologic Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1010064Subventions
Organisme : NIAID NIH HHS
ID : R01 AI056273
Pays : United States
Organisme : NIAID NIH HHS
ID : R56 AI056273
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Int Arch Allergy Immunol. 2017;174(3-4):170-182
pubmed: 29130972
Anal Chim Acta. 2018 Dec 11;1037:107-118
pubmed: 30292284
J Biol Chem. 2002 Sep 13;277(37):34329-35
pubmed: 12107158
Proteomics. 2006 Apr;6 Suppl 1:S226-36
pubmed: 16511809
Int Arch Allergy Immunol. 2000 Mar;121(3):194-204
pubmed: 10729777
Mol Biochem Parasitol. 2009 Jul;166(1):42-6
pubmed: 19428671
Exp Parasitol. 1996 Nov;84(2):168-77
pubmed: 8932766
ScientificWorldJournal. 2011 Feb 03;11:320-39
pubmed: 21298223
Am J Trop Med Hyg. 1993 Apr;48(4):496-503
pubmed: 8480857
Int J Cancer. 2002 May 20;99(3):386-95
pubmed: 11992407
Parasite Immunol. 2010 Nov-Dec;32(11-12):739-48
pubmed: 21039614
Am J Physiol Cell Physiol. 2020 May 1;318(5):C832-C835
pubmed: 32159362
PeerJ. 2014 Mar 18;2:e316
pubmed: 24711968
Mol Biochem Parasitol. 1993 Apr;58(2):205-14
pubmed: 8479445
J Immunol. 2007 May 15;178(10):6023-7
pubmed: 17475824
Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):778-81
pubmed: 1309957
Mol Cell Proteomics. 2006 May;5(5):835-44
pubmed: 16469760
J Exp Med. 2009 Aug 3;206(8):1673-80
pubmed: 19635864
J Allergy Clin Immunol. 2011 Oct;128(4):733-9
pubmed: 21684587
Biochemistry. 2005 Aug 23;44(33):11082-97
pubmed: 16101292
J Immunol Res. 2016;2016:5267485
pubmed: 27635405
Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):18-22
pubmed: 7904066
J Immunol. 2005 Aug 15;175(4):2082-90
pubmed: 16081774
J Biol Chem. 2002 Dec 13;277(50):48122-9
pubmed: 12359728
J Immunol. 1992 Apr 1;148(7):2283-90
pubmed: 1347553
PLoS Negl Trop Dis. 2013 Jul 25;7(7):e2337
pubmed: 23936568
Glycobiology. 1997 Mar;7(2):207-15
pubmed: 9134427
Exp Parasitol. 1996 Jun;83(1):73-82
pubmed: 8654554
J Exp Med. 2005 Nov 21;202(10):1319-25
pubmed: 16301741
Int J Parasitol. 2016 Jan;46(1):1-5
pubmed: 26460238
Sci Rep. 2017 Oct 10;7(1):12912
pubmed: 29018227
PLoS Negl Trop Dis. 2017 Oct 26;11(10):e0006012
pubmed: 29073139
J Infect Dis. 2017 Feb 1;215(3):378-386
pubmed: 28362903
Am J Physiol Renal Physiol. 2019 Jun 1;316(6):F1133-F1140
pubmed: 30785353
J Immunol. 2001 Jul 1;167(1):442-50
pubmed: 11418681
Sci Rep. 2018 Feb 19;8(1):3286
pubmed: 29459722
Mol Cell Proteomics. 2015 Jul;14(7):1750-69
pubmed: 25883177
FASEB J. 2008 Nov;22(11):4022-32
pubmed: 18708590
Braz J Infect Dis. 2015 Mar-Apr;19(2):196-205
pubmed: 25636189
J Biol Chem. 2003 May 16;278(20):18384-92
pubmed: 12624091
Parasitol Res. 2015 May;114(5):1865-73
pubmed: 25855345
Mol Cell Proteomics. 2007 Sep;6(9):1485-99
pubmed: 17550893
Theranostics. 2017 Aug 15;7(14):3446-3460
pubmed: 28912887
Immunology. 1978 Nov;35(5):771-8
pubmed: 309856
Mem Inst Oswaldo Cruz. 2006 Sep;101 Suppl 1:205-12
pubmed: 17308771
J Immunol. 2008 Nov 15;181(10):7106-14
pubmed: 18981131
Front Immunol. 2018 Oct 10;9:2293
pubmed: 30364177
Immunobiology. 2010 Sep-Oct;215(9-10):704-8
pubmed: 20594611
Immunity. 2018 Nov 20;49(5):801-818
pubmed: 30462997
Parasitol Res. 2016 Dec;115(12):4559-4571
pubmed: 27640151
PLoS One. 2015 Sep 04;10(9):e0137495
pubmed: 26340260
Hum Immunol. 2000 Mar;61(3):225-32
pubmed: 10689112
Front Microbiol. 2020 Aug 12;11:1973
pubmed: 32922381
FASEB J. 2000 Oct;14(13):2065-74
pubmed: 11023991
Nat Rev Immunol. 2011 Jun;11(6):403-15
pubmed: 21546914
Biol Open. 2020 Mar 24;9(3):
pubmed: 32098782
Nature. 1983 Jun 30;303(5920):810-2
pubmed: 6866081
J Immunol. 1990 Apr 1;144(7):2751-6
pubmed: 1690776
Infect Immun. 2011 Apr;79(4):1779-88
pubmed: 21220486
Mol Cell Proteomics. 2011 May;10(5):M110.005710
pubmed: 21372247
J Infect Dis. 2010 Feb 1;201(3):464-72
pubmed: 20043751
Prostaglandins Leukot Essent Fatty Acids. 2015 Apr;95:57-62
pubmed: 25687497
Thromb Haemost. 2018 Jun;118(6):979-989
pubmed: 29669386
Proc Natl Acad Sci U S A. 2020 Aug 11;117(32):19299-19309
pubmed: 32737161
Mol Biochem Parasitol. 1995 Jul;73(1-2):31-41
pubmed: 8577345
J Extracell Vesicles. 2015 Oct 05;4:28665
pubmed: 26443722
Front Med (Lausanne). 2017 Jul 19;4:104
pubmed: 28770200
Infect Immun. 2001 Jun;69(6):3646-51
pubmed: 11349025
Int J Parasitol. 2006 May 31;36(6):691-9
pubmed: 16545817
Mol Biochem Parasitol. 2009 Jul;166(1):4-14
pubmed: 19428667
Cell. 2009 Dec 11;139(6):1143-56
pubmed: 20005807
Immunity. 2004 May;20(5):623-35
pubmed: 15142530
Parasit Vectors. 2020 Mar 20;13(1):147
pubmed: 32197642
Eur J Immunol. 2019 Aug;49(8):1226-1234
pubmed: 31099896
Mol Biochem Parasitol. 2006 Feb;145(2):137-46
pubmed: 16246438
J Immunol. 2001 Oct 15;167(8):4293-302
pubmed: 11591752
Microbes Infect. 2012 Nov;14(14):1284-92
pubmed: 22634347
Front Cell Infect Microbiol. 2021 Mar 18;11:649480
pubmed: 33869080
PLoS Pathog. 2018 Feb 9;14(2):e1006870
pubmed: 29425229
Mol Pharmacol. 2010 Feb;77(2):171-84
pubmed: 19903832
Mol Cell Proteomics. 2006 Feb;5(2):347-56
pubmed: 16269422
Glycobiology. 2010 Jan;20(1):2-12
pubmed: 19748975
PLoS Pathog. 2019 Jun 4;15(6):e1007817
pubmed: 31163079
PLoS Negl Trop Dis. 2013;7(3):e2094
pubmed: 23505586
J Egypt Soc Parasitol. 2015 Dec;45(3):511-20
pubmed: 26939228
J Exp Med. 1994 May 1;179(5):1625-36
pubmed: 7513011
Int J Parasitol. 2020 Aug;50(9):685-696
pubmed: 32598872
Trends Immunol. 2004 Jan;25(1):33-9
pubmed: 14698282
Immunology. 2008 Sep;125(1):111-21
pubmed: 18373667
Contrib Microbiol Immunol. 1983;7:22-9
pubmed: 6600671
Pathog Dis. 2016 Aug;74(6):
pubmed: 27354294
Parasitology. 1985 Aug;91 ( Pt 1):111-20
pubmed: 4034241
Int J Parasitol. 2009 Jan;39(2):191-200
pubmed: 18804475
Blood. 2004 Dec 15;104(13):3986-92
pubmed: 15319286
Mol Biochem Parasitol. 2019 Sep;232:111190
pubmed: 31154018
Lancet. 2014 Jun 28;383(9936):2253-64
pubmed: 24698483
Cell Microbiol. 2004 Jan;6(1):13-22
pubmed: 14678327
Infect Immun. 1999 May;67(5):2201-8
pubmed: 10225875
Eur J Immunol. 2003 May;33(5):1439-49
pubmed: 12731071
Glycobiology. 1997 Jul;7(5):663-77
pubmed: 9254048
Parasitol Res. 2017 Mar;116(3):901-908
pubmed: 28066871
J Biol Chem. 2010 Jan 29;285(5):3383-92
pubmed: 19923225
J Immunol. 2004 Jul 15;173(2):1224-31
pubmed: 15240714
FEBS J. 2006 May;273(10):2276-92
pubmed: 16650003
PLoS Negl Trop Dis. 2014 Feb 13;8(2):e2703
pubmed: 24551263
Infect Immun. 2009 Mar;77(3):1144-54
pubmed: 19124604
Bioessays. 2019 Dec;41(12):e1900103
pubmed: 31661165
J Exp Med. 2012 Sep 24;209(10):1753-67, S1
pubmed: 22966004
Biochim Biophys Acta Mol Cell Biol Lipids. 2017 Feb;1862(2):246-254
pubmed: 27871882
Infect Immun. 2017 Nov 17;85(12):
pubmed: 28923894
Parasit Vectors. 2017 Feb 17;10(1):89
pubmed: 28212670
PLoS Negl Trop Dis. 2008 Oct 01;2(10):e308
pubmed: 18827884
Trends Parasitol. 2009 Jun;25(6):256-60
pubmed: 19423396
Parasit Vectors. 2016 Jan 04;9:6
pubmed: 26728323
Parasite Immunol. 2001 Mar;23(3):141-52
pubmed: 11240905
Front Immunol. 2018 Nov 14;9:2614
pubmed: 30487793
Front Immunol. 2019 Jan 09;9:3122
pubmed: 30687325
Vet Immunol Immunopathol. 2013 Apr 15;152(3-4):269-76
pubmed: 23340445
EMBO Rep. 2020 Jan 7;21(1):e47882
pubmed: 31825165
Exp Parasitol. 2011 Nov;129(3):284-91
pubmed: 21784070
Parasite Immunol. 2012 Aug-Sep;34(8-9):430-9
pubmed: 22712636
Mol Biochem Parasitol. 2006 May;147(1):9-19
pubmed: 16480783
Int J Cell Cloning. 1991 Sep;9(5):438-50
pubmed: 1955735
J Proteomics. 2016 Jan 1;130:221-30
pubmed: 26453986
J Biol Chem. 2002 Aug 23;277(34):31207-13
pubmed: 12050167
Infect Immun. 2013 Jan;81(1):133-42
pubmed: 23090958
PLoS Pathog. 2015 Dec 11;11(12):e1005335
pubmed: 26658895
J Parasitol. 2006 Dec;92(6):1365-9
pubmed: 17304823
Mol Biochem Parasitol. 2017 Jul;215:40-46
pubmed: 28011341
Mol Biochem Parasitol. 2009 Mar;164(1):26-31
pubmed: 19041905
Blood. 1996 Dec 1;88(11):4246-51
pubmed: 8943860
Infect Immun. 2005 Jan;73(1):395-402
pubmed: 15618177
Int J Parasitol. 2015 Nov;45(13):809-13
pubmed: 26385440
Thromb Res. 2014 Dec;134(6):1176-81
pubmed: 25294585
PLoS Negl Trop Dis. 2011 Oct;5(10):e1368
pubmed: 22039561
Exp Parasitol. 2013 Sep;135(1):64-71
pubmed: 23756146
Mol Biochem Parasitol. 2007 Oct;155(2):84-93
pubmed: 17644200
Trends Parasitol. 2005 May;21(5):201-3
pubmed: 15837605
Springer Semin Immunopathol. 2005 Nov;27(3):320-31
pubmed: 16235057
Infect Immun. 2003 Nov;71(11):6402-10
pubmed: 14573661
PLoS Negl Trop Dis. 2020 Jul 9;14(7):e0008470
pubmed: 32644998
Biochim Biophys Acta. 1999 Oct 8;1455(2-3):363-74
pubmed: 10571025
Res Pract Thromb Haemost. 2018 Dec 16;3(1):38-43
pubmed: 30656274
Front Genet. 2014 Aug 05;5:262
pubmed: 25147556
Front Immunol. 2020 Feb 18;11:61
pubmed: 32132991
Immunity. 2017 Jul 18;47(1):15-31
pubmed: 28723547
PLoS One. 2012;7(2):e30883
pubmed: 22347409
Sci Rep. 2016 May 13;6:25885
pubmed: 27172881
J Inflamm. 1995-1996;46(1):13-22
pubmed: 8832968
J Immunol. 1999 Oct 15;163(8):4140-9
pubmed: 10510349
Front Immunol. 2018 Dec 20;9:3042
pubmed: 30619372
Parasite Immunol. 2014 Aug;36(8):347-57
pubmed: 25142505
J Exp Med. 2001 May 21;193(10):1135-47
pubmed: 11369785
J Biol Chem. 2005 Jan 7;280(1):277-83
pubmed: 15519998
J Exp Med. 1991 Dec 1;174(6):1399-406
pubmed: 1720809
PLoS Negl Trop Dis. 2013 Oct 24;7(10):e2482
pubmed: 24205416
J Immunol. 1988 Jun 1;140(11):3962-5
pubmed: 3131420
Pharmacol Ther. 2006 Nov;112(2):358-404
pubmed: 16784779
Virulence. 2020 Dec;11(1):568-579
pubmed: 32441549
PLoS Negl Trop Dis. 2011 Apr 05;5(4):e1011
pubmed: 21483710
Gene Ther. 2002 Jan;9(1):38-45
pubmed: 11850721
Mol Cell Proteomics. 2009 Jun;8(6):1236-51
pubmed: 19299421
Int J Parasitol. 2010 Apr;40(5):617-28
pubmed: 19917288
Parasit Vectors. 2015 Jan 06;8:1
pubmed: 25561160
Mol Biochem Parasitol. 2011 Sep;179(1):18-29
pubmed: 21605600
Exp Parasitol. 1996 Mar;82(2):191-200
pubmed: 8617346
Biochem Biophys Res Commun. 2003 Aug 8;307(4):831-8
pubmed: 12878186
Exp Parasitol. 1987 Dec;64(3):361-7
pubmed: 2824233
Parasite Immunol. 1990 Mar;12(2):189-98
pubmed: 2108424
Parasitology. 1994 May;108 ( Pt 4):433-46
pubmed: 7516535
FASEB J. 2021 Feb;35(2):e21331
pubmed: 33476078
Infect Immun. 2011 Oct;79(10):4276-84
pubmed: 21825060
Semin Immunopathol. 2012 Nov;34(6):863-71
pubmed: 23139101
Elife. 2019 Jan 15;8:
pubmed: 30644357
J Immunol. 1992 Sep 1;149(5):1714-22
pubmed: 1387150
J Proteome Res. 2005 May-Jun;4(3):958-66
pubmed: 15952743
Int J Parasitol. 2015 Aug;45(9-10):629-36
pubmed: 25975668
Front Immunol. 2019 May 07;10:1010
pubmed: 31134080
J Biol Chem. 2015 Sep 4;290(36):22111-26
pubmed: 26163514
PLoS Pathog. 2017 Jul 28;13(7):e1006539
pubmed: 28753651
Glycobiology. 1998 Jun;8(6):615-24
pubmed: 9592128
Mol Biochem Parasitol. 1998 Oct 30;96(1-2):49-58
pubmed: 9851606
J Immunol. 2007 Jul 1;179(1):186-94
pubmed: 17579037
J Immunol. 1993 Dec 15;151(12):7057-66
pubmed: 8258710
Trans R Soc Trop Med Hyg. 1984;78(3):385-8
pubmed: 6464135
J Biol Chem. 1996 Sep 6;271(36):22139-45
pubmed: 8703025
J Immunol. 2001 Nov 1;167(9):5294-303
pubmed: 11673545
Mol Biochem Parasitol. 2007 Dec;156(2):225-34
pubmed: 17913257
Sci Rep. 2019 Feb 7;9(1):1586
pubmed: 30733505
Parasit Vectors. 2018 Mar 14;11(1):182
pubmed: 29540224
Nat Rev Immunol. 2002 Jul;2(7):499-511
pubmed: 12094224
Mol Cell Probes. 2011 Aug;25(4):186-93
pubmed: 21601634
Mol Biochem Parasitol. 2005 Nov;144(1):123-7
pubmed: 16143411
Infect Immun. 2012 Dec;80(12):4264-70
pubmed: 23006852
FASEB J. 2016 Feb;30(2):824-35
pubmed: 26490658
Cell Microbiol. 2018 May;20(5):e12836
pubmed: 29498184
J Immunol. 2012 Jan 1;188(1):21-8
pubmed: 22187483
J Exp Med. 2009 Aug 3;206(8):1681-90
pubmed: 19635859
Parasite Immunol. 2010 May;32(5):345-53
pubmed: 20500663
Eur J Immunol. 2009 Apr;39(4):1098-107
pubmed: 19291704
Am J Trop Med Hyg. 1980 Sep;29(5):886-9
pubmed: 6159797
Nat Commun. 2014 Nov 17;5:5375
pubmed: 25400038
J Immunol. 2004 Jul 15;173(2):932-44
pubmed: 15240680
Biochimie. 2016 Mar;122:99-109
pubmed: 26409899
Sci Am. 2008 May;298(5):94-9
pubmed: 18444331
Science. 1986 Jan 10;231(4734):153-6
pubmed: 3079916
J Biol Chem. 2012 Aug 17;287(34):28435-44
pubmed: 22761438
PLoS Pathog. 2007 Apr;3(4):e52
pubmed: 17411340
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009 Jun 1;65(Pt 6):594-6
pubmed: 19478439
PLoS Pathog. 2016 Nov 2;12(11):e1005991
pubmed: 27806135
PLoS Biol. 2018 Oct 31;16(10):e2005850
pubmed: 30379806
Trends Immunol. 2005 Jun;26(6):299-304
pubmed: 15922945
J Immunol. 2000 Oct 15;165(8):4567-74
pubmed: 11035098
J Immunol Res. 2019 Dec 1;2019:6793596
pubmed: 31886307
FEBS Lett. 2000 Mar 24;470(2):131-4
pubmed: 10734221
Parasitology. 1991 Oct;103 Pt 2:225-36
pubmed: 1745548
J Immunol. 1991 Feb 15;146(4):1322-7
pubmed: 1825109
Exp Parasitol. 1985 Feb;59(1):44-50
pubmed: 3917929
PLoS Negl Trop Dis. 2011 Mar 29;5(3):e993
pubmed: 21468311
PLoS Biol. 2018 Apr 18;16(4):e2005504
pubmed: 29668708
Mol Biochem Parasitol. 2020 Mar;236:111264
pubmed: 32014446
J Proteomics. 2016 Apr 14;138:30-9
pubmed: 26915583
Immunol Rev. 2004 Oct;201:117-26
pubmed: 15361236
Parasitol Res. 2012 Jun;110(6):2429-37
pubmed: 22281546
Parasitol Today. 1987 Sep;3(9):279-81
pubmed: 15462982
Front Immunol. 2018 Jul 30;9:1746
pubmed: 30105025
Parasite Immunol. 2009 Apr;31(4):163-76
pubmed: 19292768
Parasitology. 2001 Mar;122(Pt 3):329-38
pubmed: 11289069
Front Immunol. 2019 Jan 25;9:3161
pubmed: 30740113
Front Immunol. 2018 Oct 29;9:2492
pubmed: 30459767
Mol Biochem Parasitol. 2009 Jul;166(1):32-41
pubmed: 19428670
Science. 2018 Jan 5;359(6371):114-119
pubmed: 29302015
Sci Rep. 2015 Aug 24;5:13434
pubmed: 26299686