Src- and Abl-family kinases activate spleen tyrosine kinase to maximize phagocytosis and Leishmania infection.
Leishmania
Kinase
Macrophage
Parasite
Pathogen
Journal
Journal of cell science
ISSN: 1477-9137
Titre abrégé: J Cell Sci
Pays: England
ID NLM: 0052457
Informations de publication
Date de publication:
15 07 2023
15 07 2023
Historique:
received:
17
11
2022
accepted:
19
06
2023
medline:
31
7
2023
pubmed:
26
6
2023
entrez:
26
6
2023
Statut:
ppublish
Résumé
Leishmania spp. are obligate intracellular parasites that must be internalized by phagocytic cells to evade immune responses and cause disease. The uptake of both Leishmania promastigotes (insect-stage parasites) and amastigotes (proliferative-stage parasites in humans and mice) by phagocytes is thought to be mainly host cell driven, not parasite driven. Our previous work indicates that host Src- and Abl-family kinases facilitate Leishmania entry into macrophages and pathogenesis in murine cutaneous leishmaniasis. Here, we demonstrate that host spleen tyrosine kinase (SYK) is required for efficient uptake of Leishmania promastigotes and amastigotes. A Src-family kinase-Abl-family kinase-SYK signaling cascade induces Leishmania amastigote internalization. Finally, lesion size and parasite burden during Leishmania infection is significantly decreased in mice lacking SYK in monocytes or by treatment with the SYK inhibitor entospletinib. In summary, SYK is required for maximal Leishmania uptake by macrophages and disease in mice. Our results suggest potential for treating leishmaniasis using host cell-directed agents.
Identifiants
pubmed: 37357611
pii: 319895
doi: 10.1242/jcs.260809
pmc: PMC10399977
pii:
doi:
Substances chimiques
Syk Kinase
EC 2.7.10.2
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
Subventions
Organisme : NIAID NIH HHS
ID : K08 AI103036
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI146349
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008014
Pays : United States
Organisme : NIH HHS
ID : K08 AI103036
Pays : United States
Informations de copyright
© 2023. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
Références
EMBO J. 1998 Aug 17;17(16):4606-16
pubmed: 9707420
J Exp Med. 2000 Mar 20;191(6):1063-8
pubmed: 10727468
Mol Immunol. 2008 May;45(10):3012-21
pubmed: 18295889
Mol Cell Biol. 2012 Aug;32(15):3176-86
pubmed: 22665498
J Exp Med. 2008 Sep 29;205(10):2339-47
pubmed: 18794338
J Immunol. 2012 Dec 1;189(11):5382-92
pubmed: 23100514
J Cell Sci. 2016 Aug 15;129(16):3130-43
pubmed: 27358479
Cancer Res. 2011 Mar 1;71(5):1730-41
pubmed: 21257711
Blood. 2001 Jun 15;97(12):3836-45
pubmed: 11389024
Biochim Biophys Acta. 1997 Feb 4;1355(2):177-90
pubmed: 9042338
Cell Signal. 2010 Aug;22(8):1175-84
pubmed: 20206686
J Exp Med. 1988 Jul 1;168(1):279-92
pubmed: 3294332
Front Biosci. 1998 Nov 15;3:D1171-80
pubmed: 9820738
Blood. 2004 Dec 1;104(12):3766-73
pubmed: 15304396
Nat Commun. 2022 Mar 11;13(1):1295
pubmed: 35277504
J Biol Chem. 2021 Jan-Jun;296:100256
pubmed: 33839682
Proc Natl Acad Sci U S A. 2012 Jan 24;109(4):1251-6
pubmed: 22232690
Mol Cell Biol. 2003 Jun;23(11):3884-96
pubmed: 12748290
J Exp Med. 2000 Feb 21;191(4):669-82
pubmed: 10684859
ACS Infect Dis. 2020 Aug 14;6(8):2057-2072
pubmed: 32686409
Nat Commun. 2021 Feb 23;12(1):1244
pubmed: 33623024
Mol Cell Biol. 2004 Mar;24(6):2573-83
pubmed: 14993293
Clin Drug Investig. 2017 Feb;37(2):195-205
pubmed: 27785737
FEBS Lett. 2000 Feb 11;467(2-3):253-8
pubmed: 10675549
Mol Cell Biol. 1998 Jul;18(7):4209-20
pubmed: 9632805
Infect Immun. 2005 Sep;73(9):5379-87
pubmed: 16113253
Trends Parasitol. 2012 Aug;28(8):335-44
pubmed: 22726697
J Cell Sci. 2004 Nov 15;117(Pt 24):5739-48
pubmed: 15507483
J Leukoc Biol. 1999 Jun;65(6):854-62
pubmed: 10380910
IUBMB Life. 2006 May-Jun;58(5-6):304-8
pubmed: 16754322
Clin Cancer Res. 2020 Nov 15;26(22):5852-5859
pubmed: 32820015
Subcell Biochem. 2008;47:174-81
pubmed: 18512351
BMC Genomics. 2005 Sep 15;6:127
pubmed: 16164760
J Biol Chem. 2015 Oct 30;290(44):26422-9
pubmed: 26354432
J Immunol. 1997 Jun 1;158(11):5374-83
pubmed: 9164958
J Exp Med. 1997 Oct 6;186(7):1027-39
pubmed: 9314552
J Biol Chem. 2015 Jul 10;290(28):17306-20
pubmed: 26032420
J Immunol. 1988 Apr 1;140(7):2406-14
pubmed: 2450920
Infect Immun. 1993 Apr;61(4):1553-8
pubmed: 8454363
Cold Spring Harb Perspect Biol. 2011 Mar 01;3(3):
pubmed: 21068150
Nat Rev Immunol. 2010 Jun;10(6):387-402
pubmed: 20467426
Exp Parasitol. 1996 Jun;83(1):94-105
pubmed: 8654556
J Cell Biol. 1992 Jan;116(2):511-20
pubmed: 1730765
Mol Biol Cell. 2003 Feb;14(2):396-406
pubmed: 12589042
Nat Med. 2013 Jul;19(7):909-15
pubmed: 23749230
J Cell Sci. 2009 Oct 1;122(Pt 19):3441-54
pubmed: 19759284
J Exp Med. 1988 Mar 1;167(3):887-902
pubmed: 3280727