ATP6V(0)d2 controls Leishmania parasitophorous vacuole biogenesis via cholesterol homeostasis
Carregando...
Citações na Scopus
18
Tipo de produção
article
Data de publicação
2019
Título da Revista
ISSN da Revista
Título do Volume
Editora
PUBLIC LIBRARY SCIENCE
Autores
PESSOA, Carina Carraro
ORIKAZA, Cristina Mary
CORTEZ, Cristian
LEVATTI, Erica Valadares de Castro
BADARO, Ana Carolina Benites
YAMAMOTO, Joyce Umbelino da Silva
D'ALMEIDA, Vania
Citação
PLOS PATHOGENS, v.15, n.6, article ID e1007834, 32p, 2019
Resumo
V-ATPases are part of the membrane components of pathogen-containing vacuoles, although their function in intracellular infection remains elusive. In addition to organelle acidification, V-ATPases are alternatively implicated in membrane fusion and anti-inflammatory functions controlled by ATP6V(0)d2, the d subunit variant of the V-ATPase complex. Therefore, we evaluated the role of ATP6V(0)d2 in the biogenesis of pathogen-containing vacuoles using ATP6V(0)d2 knock-down macrophages infected with the protozoan parasite Leishmania amazonensis. These parasites survive within IFN gamma/LPS-activated inflammatory macrophages, multiplying in large/fusogenic parasitophorous vacuoles (PVs) and inducing ATP6V(0)d2 upregulation. ATP6V(0)d2 knock-down decreased macrophage cholesterol levels and inhibited PV enlargement without interfering with parasite multiplication. However, parasites required ATP6V(0)d2 to resist the influx of oxidized low-density lipoprotein (ox-LDL)-derived cholesterol, which restored PV enlargement in ATP6V(0)d2 knock-down macrophages by replenishing macrophage cholesterol pools. Thus, we reveal parasite-mediated subversion of host V-ATPase function toward cholesterol retention, which is required for establishing an inflammation-resistant intracellular parasite niche. Author summary V-ATPases control acidification and other processes at intracellular vesicles that bacteria and parasites exploit as compartments for replication and immune evasion. We report that the protozoan intracellular parasite Leishmania amazonensis resists inflammatory macrophage immune responses and upregulates an alternative isoform of subunit d of V-ATPase (ATP6V(0)d2). Leishmania are still sequestered within acidified parasitophorous vacuoles (PVs) in cells lacking ATP6V(0)d2, but these PVs do not enlarge in volume, a distinguishing feature of intracellular infection by these parasites. Cholesterol levels in ATP6V(0)d2-deficient cells are reduced and exogenous cholesterol repletion can restore vacuole size, leading to enhanced parasite killing. This study demonstrates the ATP6V(0)d2-mediated interplay of macrophage cholesterol retention and control of the biogenesis of large pathogen-containing vacuoles. The study provides grounds for the development of new therapeutic strategies for diseases caused by intracellular pathogens sheltered in host cell compartments.
Palavras-chave
Referências
- Aflaki E, 2014, SCI TRANSL MED, V6, DOI 10.1126/scitranslmed.3008659
- Alexander J, 1999, J CELL SCI, V112, P2993
- Andrade-Neto VV, 2011, ACTA TROP, V119, P194, DOI 10.1016/j.actatropica.2011.05.001
- ARANDA CMA, 1992, P NATL ACAD SCI USA, V89, P10079, DOI 10.1073/pnas.89.21.10079
- Attie AD, 2005, CELL METAB, V1, P290, DOI 10.1016/j.cmet.2005.04.006
- BARRAL A, 1995, INT J DERMATOL, V34, P474, DOI 10.1111/j.1365-4362.1995.tb00613.x
- Bogdan C, 2000, CURR OPIN IMMUNOL, V12, P64, DOI 10.1016/S0952-7915(99)00052-7
- BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1006/abio.1976.9999
- Bustin SA, 2009, CLIN CHEM, V55, P611, DOI 10.1373/clinchem.2008.112797
- Casgrain PA, 2016, PLOS PATHOG, V12, DOI 10.1371/journal.ppat.1005658
- Christian AE, 1997, J LIPID RES, V38, P2264
- Comert M, 2004, J GASTROEN HEPATOL, V19, P1052, DOI 10.1111/j.1440-1746.2004.03400.x
- Coppens I, 2000, J CELL BIOL, V149, P167, DOI 10.1083/jcb.149.1.167
- Cotter K, 2015, TRENDS BIOCHEM SCI, V40, P611, DOI 10.1016/j.tibs.2015.08.005
- De Cicco NNT, 2012, EXP PARASITOL, V130, P330, DOI 10.1016/j.exppara.2012.02.014
- Demaurex N, 2006, CELL BIOL, P163
- Di Giovanni J, 2010, NEURON, V67, P268, DOI 10.1016/j.neuron.2010.06.024
- Diaz NL, 2006, CLIN EXP DERMATOL, V31, P114, DOI 10.1111/j.1365-2230.2005.01991.x
- Dweik RA, 1998, J CLIN INVEST, V101, P660, DOI 10.1172/JCI1378
- Ehrenman K, 2013, CELL MICROBIOL, V15, P1182, DOI 10.1111/cmi.12107
- Forgac M, 2007, NAT REV MOL CELL BIO, V8, P917, DOI 10.1038/nrm2272
- Fujita K, 2012, NAT MED, V18, P589, DOI 10.1038/nm.2659
- Galle J, 2006, ATHEROSCLEROSIS, V185, P219, DOI 10.1016/j.atherosclerosis.2005.10.005
- Goldstein JL, 2006, CELL, V124, P35, DOI 10.1016/j.cell.2005.12.022
- Goncalves VM, 2014, MICROBES INFECT, V16, P253, DOI 10.1016/j.micinf.2013.11.004
- Haidar B, 2006, J BIOL CHEM, V281, P39971, DOI 10.1074/jbc.M605095200
- Hamilton J, 2012, CLIN CHIM ACTA, V413, P1207, DOI 10.1016/j.cca.2012.03.019
- Han JH, 1999, J LIPID RES, V40, P830
- Heinrich M, 2000, ADV EXP MED BIOL, V477, P305
- Henard CA, 2014, PLOS NEGLECT TROP D, V8, DOI 10.1371/journal.pntd.0003000
- Houben T, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-03796-5
- Huynh KK, 2007, MICROBIOL MOL BIOL R, V71, P452, DOI 10.1128/MMBR.00003-07
- Jongstra-Bilen J, 2017, J IMMUNOL, V199, P2149, DOI 10.4049/jimmunol.1601363
- Jung M, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0116972
- Kane PA, 2006, MICROBIOL MOL BIOL R, V70, P177, DOI 10.1128/MMBR.70.1.177-191.2006
- Kawasaki-Nishi S, 2001, J BIOL CHEM, V276, P47411, DOI 10.1074/jbc.M108310200
- Kissing S, 2015, J BIOL CHEM, V290, P14166, DOI 10.1074/jbc.M114.628891
- Koller D, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0110486
- KOLODNY EH, 1976, CLIN CHIM ACTA, V70, P247, DOI 10.1016/0009-8981(76)90426-5
- LEAO SD, 1995, J CELL SCI, V108, P3219
- Lee SH, 2006, NAT MED, V12, P1403, DOI 10.1038/nm1514
- Liu FY, 2016, ONCOTARGET, V7, P83907, DOI 10.18632/oncotarget.13438
- Livak KJ, 2001, METHODS, V25, P402, DOI 10.1006/meth.2001.1262
- Lizio M, 2015, GENOME BIOL, V16, DOI 10.1186/s13059-014-0560-6
- LUKACS GL, 1990, J BIOL CHEM, V265, P21099
- Madison BB, 2016, J LIPID RES, V57, P333, DOI 10.1194/jlr.C066712
- MANOLSON MF, 1994, J BIOL CHEM, V269, P14064
- Marshansky V, 2008, CURR OPIN CELL BIOL, V20, P415, DOI 10.1016/j.ceb.2008.03.015
- Martinez Fernando O, 2014, F1000Prime Rep, V6, P13, DOI 10.12703/P6-13
- Matheoud D, 2013, CELL HOST MICROBE, V14, P15, DOI 10.1016/j.chom.2013.06.003
- Maxson ME, 2014, J CELL SCI, V127, P4987, DOI 10.1242/jcs.158550
- Mindell JA, 2012, ANNU REV PHYSIOL, V74, P69, DOI 10.1146/annurev-physiol-012110-142317
- Miyamoto Takeshi, 2013, JAKSTAT, V2, pe24777, DOI 10.4161/jkst.24777
- Moore KJ, 2013, NAT REV IMMUNOL, V13, P709, DOI 10.1038/nri3520
- Mukbel RM, 2007, AM J TROP MED HYG, V76, P669, DOI 10.4269/ajtmh.2007.76.669
- Munder M, 2009, BRIT J PHARMACOL, V158, P638, DOI 10.1111/j.1476-5381.2009.00291.x
- Murase M, 2018, J IMMUNOL, V200, P2798, DOI 10.4049/jimmunol.1701390
- Okuda K, 2016, PLOS PATHOG, V12, DOI 10.1371/journal.ppat.1005669
- Osorio y Fortea Jose, 2009, BMC Genomics, V10, P119, DOI 10.1186/1471-2164-10-119
- Pennings M, 2006, FEBS LETT, V580, P5588, DOI 10.1016/j.febslet.2006.08.022
- Pfaffl MW, 2001, NUCLEIC ACIDS RES, V29, DOI 10.1093/nar/29.9.e45
- Poea-Guyon S, 2013, J CELL BIOL, V203, P283, DOI 10.1083/jcb.201303104
- Pryor PR, 2004, EMBO REP, V5, P590, DOI 10.1038/sj.embor.7400150
- Puri V, 1999, NAT CELL BIOL, V1, P386
- Qi H, 2004, INFECT IMMUN, V72, P988, DOI 10.1128/IAI.72.2.988-995.2004
- RABINOVITCH M, 1982, J EXP MED, V155, P415, DOI 10.1084/jem.155.2.415
- RAGHAVAN SS, 1980, AM J HUM GENET, V32, P158
- Real F, 2014, CELL MICROBIOL, V16, P1549, DOI 10.1111/cmi.12311
- Real F, 2012, PLOS NEGLECT TROP D, V6, DOI 10.1371/journal.pntd.0001518
- Real F, 2010, PLOS NEGLECT TROP D, V4, DOI 10.1371/journal.pntd.0000905
- Roberts CW, 2003, MOL BIOCHEM PARASIT, V126, P129, DOI 10.1016/S0166-6851(02)00280-3
- Roth KS, 2017, PEDIAT ENDOCRINOLOGY
- Russell DG, 2009, NAT IMMUNOL, V10, P943, DOI 10.1038/ni.1781
- Sacks D, 2002, NAT REV IMMUNOL, V2, P845, DOI 10.1038/nri933
- Sacks D, 2002, NAT IMMUNOL, V3, P1041, DOI 10.1038/ni1102-1041
- SCOTT P, 1986, J IMMUNOL, V136, P1461
- Semini G, 2017, MICROBIOLOGYOPEN, V6, DOI 10.1002/mbo3.469
- Smith AN, 2005, J AM SOC NEPHROL, V16, P1245, DOI 10.1681/ASN.2004090761
- Soldati T, 2012, TRAFFIC, V13, P1042, DOI 10.1111/j.1600-0854.2012.01358.x
- Soong L, 2012, SEMIN IMMUNOPATHOL, V34, P735, DOI 10.1007/s00281-012-0350-8
- Soong L, 2012, FRONT IMMUNOL, V3, DOI 10.3389/fimmu.2012.00058
- Steinberg D, 1997, J BIOL CHEM, V272, P20963, DOI 10.1074/jbc.272.34.20963
- Steinbrecher UP, 1999, BBA-MOL CELL BIOL L, V1436, P279, DOI 10.1016/S0005-2760(98)00127-1
- Stoka V, 2016, AGEING RES REV, V32, P22, DOI 10.1016/j.arr.2016.04.010
- STRAUS AH, 1993, J BIOL CHEM, V268, P13723
- STURGILLKOSZYCKI S, 1994, SCIENCE, V263, P678, DOI 10.1126/science.8303277
- Tekin NS, 2007, MEDIAT INFLAMM, DOI 10.1155/2007/78454
- Toledo DAM, 2016, FRONT IMMUNOL, V7, DOI 10.3389/fimmu.2016.00174
- Tsukano H, 1999, MICROB PATHOGENESIS, V27, P253, DOI 10.1006/mpat.1999.0303
- Vieira OV, 2002, BIOCHEM J, V366, P689, DOI 10.1042/BJ20020691
- Wang YG, 2015, J GERIATR CARDIOL, V12, P410, DOI 10.11909/j.issn.1671-5411.2015.04.013
- Watterson S, 2013, BIOCHIMIE, V95, P613, DOI 10.1016/j.biochi.2012.05.024
- Wilson J, 2008, PLOS PATHOG, V4, DOI 10.1371/journal.ppat.1000179
- Wong D, 2011, P NATL ACAD SCI USA, V108, P19371, DOI 10.1073/pnas.1109201108
- Wu HP, 2009, J BONE MINER RES, V24, P871, DOI [10.1359/JBMR.081239, 10.1359/jbmr.081239]
- Xia Y, 2019, AUTOPHAGY, P1, DOI [10.1080/15548627.2019.1569916, DOI 10.1080/15548627.2019.156991630681394]
- Xu L, 2010, PLOS PATHOG, V6, DOI 10.1371/journal.ppat.1000822
- Ylitalo R, 1999, LIFE SCI, V64, P1955, DOI 10.1016/S0024-3205(99)00140-X
- 2010, WHO TECH REP SER, V949, P1