Abstract
Chagas disease courses with different clinical phases and has a variable clinical presentation and progression. The acute infection phase mostly exhibits a non-specific symptomatology. In the absence of treatment, the acute phase is followed by a chronic phase, which is initially asymptomatic. This chronic asymptomatic phase of the disease is characterized by a fragile balance between the host’s immune response and the parasite replication. The loss of this balance is crucial for the progression of the sickness. The virulence and tropism of the T. cruzi infecting strain together to the inflammation processes in the cardiac tissue are the main factors for the establishment and severity of the cardiomyopathy. The efficacy of treatment in chronic Chagas disease patients is controversial. However, several studies carried out in chronic patients demonstrated that antiparasitic treatment reduces parasite load in the bloodstream and leads to an improvement in the immune response against the Trypanosoma cruzi parasite. The present review is mainly focused on the cellular patterns associated to the clinical status and the evolution of the disease in chronic patients, as well as the effectiveness of the treatment related to T. cruzi infection control. Therefore, an emphasis is placed on the dynamics of specific-antigens T cell subpopulations, their memory and activation phenotypes, their functionality and their contribution to pathogenesis or disease control, as well as their association with risk of congenital transmission of the parasite.
Keywords: Chagas disease, Trypanosoma cruzi, trypanocidal treatment, biomarker, immune response, CD8 and CD4 T cells, CTL epitopes, vertical transmission.
[http://dx.doi.org/10.1016/S0140-6736(10)60061-X] [PMID: 20399979]
[http://dx.doi.org/10.1007/s00281-015-0481-9] [PMID: 25921214]
[http://dx.doi.org/10.1016/j.actatropica.2009.11.003] [PMID: 19932071]
[http://dx.doi.org/10.1016/j.actatropica.2009.07.019] [PMID: 19646412]
[http://dx.doi.org/10.1056/NEJM200011093431908] [PMID: 11070105]
[http://dx.doi.org/10.1590/S0074-02762009000900006] [PMID: 19753455]
[http://dx.doi.org/10.1016/S1473-3099(13)70002-1] [PMID: 23395248]
[PMID: 25671846]
[http://dx.doi.org/10.1086/651608] [PMID: 20307205]
[http://dx.doi.org/10.1111/j.1537-2995.2008.01789.x] [PMID: 18522707]
[http://dx.doi.org/10.1590/S0074-02762007005000093] [PMID: 17891282]
[http://dx.doi.org/10.1371/journal.pntd.0002300] [PMID: 24205411]
[http://dx.doi.org/10.1371/journal.pntd.0003540] [PMID: 25680190]
[PMID: 21944556]
[http://dx.doi.org/10.1371/journal.pntd.0001962] [PMID: 23301105]
[http://dx.doi.org/10.3389/fimmu.2015.00659] [PMID: 26834737]
[http://dx.doi.org/10.1155/2014/243786] [PMID: 25104879]
[http://dx.doi.org/10.1016/S0300-8932(09)73074-X] [PMID: 19889333]
[http://dx.doi.org/10.1371/journal.pone.0141847] [PMID: 26599761]
[http://dx.doi.org/10.1016/S1473-3099(01)00065-2] [PMID: 11871482]
[http://dx.doi.org/10.1016/j.pt.2005.09.007] [PMID: 16236550]
[http://dx.doi.org/10.1128/AAC.01662-13] [PMID: 24247135]
[http://dx.doi.org/10.1128/AAC.49.4.1521-1528.2005] [PMID: 15793134]
[http://dx.doi.org/10.1128/CVI.00274-12] [PMID: 22739694]
[http://dx.doi.org/10.1056/NEJMoa1507574] [PMID: 26323937]
[http://dx.doi.org/10.1016/j.actatropica.2016.09.010] [PMID: 27619190]
[http://dx.doi.org/10.1016/j.ijantimicag.2007.01.014] [PMID: 17395432]
[http://dx.doi.org/10.1371/journal.pntd.0004508] [PMID: 26974551]
[http://dx.doi.org/10.1590/0074-02760140386] [PMID: 25993507]
[http://dx.doi.org/10.1001/jama.298.18.2171] [PMID: 18000201]
[PMID: 12092045]
[http://dx.doi.org/10.2174/1574891X11666161024165304] [PMID: 27784230]
[http://dx.doi.org/10.1371/journal.pntd.0001250] [PMID: 22039554]
[http://dx.doi.org/10.1586/14787210.7.2.157] [PMID: 19254164]
[http://dx.doi.org/10.1590/S0037-86822007000100001] [PMID: 17486245]
[http://dx.doi.org/10.7326/0003-4819-144-10-200605160-00006] [PMID: 16702588]
[PMID: 4998154]
[http://dx.doi.org/10.1016/j.diagmicrobio.2003.10.011] [PMID: 15062917]
[http://dx.doi.org/10.1371/journal.pntd.0002000] [PMID: 23350002]
[http://dx.doi.org/10.1590/0074-02760140435] [PMID: 25946151]
[http://dx.doi.org/10.1016/j.csbj.2016.12.002] [PMID: 28066534]
[http://dx.doi.org/10.1186/1471-2334-11-206] [PMID: 21801456]
[http://dx.doi.org/10.1093/jac/dkw090] [PMID: 27073267]
[http://dx.doi.org/10.1016/j.actatropica.2014.08.006] [PMID: 25149352]
[http://dx.doi.org/10.1128/CVI.05566-11] [PMID: 22155766]
[http://dx.doi.org/10.1017/S1462399410001560] [PMID: 20840799]
[http://dx.doi.org/10.4049/jimmunol.181.2.1333] [PMID: 18606688]
[http://dx.doi.org/10.1016/S0161-5890(02)00101-3] [PMID: 12200050]
[http://dx.doi.org/10.1038/nri1250] [PMID: 14647477]
[http://dx.doi.org/10.1016/j.coi.2007.06.003] [PMID: 17651955]
[http://dx.doi.org/10.1111/j.0105-2896.2004.00183.x] [PMID: 15361249]
[http://dx.doi.org/10.1093/nar/gki357] [PMID: 15980443]
[http://dx.doi.org/10.1080/21645515.2015.1061160] [PMID: 26107442]
[http://dx.doi.org/10.1016/j.molimm.2012.05.021] [PMID: 22750229]
[http://dx.doi.org/10.1016/j.micinf.2005.01.001] [PMID: 15848276]
[http://dx.doi.org/10.1590/S0074-02762011000100014] [PMID: 21340361]
[http://dx.doi.org/10.1371/journal.ppat.0020077] [PMID: 16879036]
[http://dx.doi.org/10.1016/j.immuni.2006.09.005] [PMID: 17046682]
[http://dx.doi.org/10.1146/annurev.immunol.17.1.51] [PMID: 10358753]
[http://dx.doi.org/10.1007/s00726-010-0579-2] [PMID: 20379752]
[PMID: 9550413]
[http://dx.doi.org/10.1093/intimm/dxh387] [PMID: 16431876]
[http://dx.doi.org/10.4049/jimmunol.1000432] [PMID: 20530265]
[http://dx.doi.org/10.1111/j.1365-3024.2005.00815.x] [PMID: 16441508]
[http://dx.doi.org/10.1111/j.1365-3024.2010.01206.x] [PMID: 20591120]
[http://dx.doi.org/10.1016/j.micinf.2011.05.010] [PMID: 21704723]
[http://dx.doi.org/10.1371/journal.pone.0122115] [PMID: 25816096]
[http://dx.doi.org/10.1128/JVI.01841-12] [PMID: 23015716]
[http://dx.doi.org/10.1002/eji.200737365] [PMID: 17705138]
[http://dx.doi.org/10.4049/jimmunol.181.4.2644] [PMID: 18684955]
[http://dx.doi.org/10.1128/JVI.78.11.5535-5545.2004] [PMID: 15140950]
[http://dx.doi.org/10.1182/blood-2002-07-2103] [PMID: 12433688]
[http://dx.doi.org/10.2217/imt.12.33] [PMID: 22642331]
[http://dx.doi.org/10.1038/nm1744] [PMID: 18425131]
[http://dx.doi.org/10.1016/j.exppara.2009.09.006] [PMID: 19747482]
[http://dx.doi.org/10.1128/CMR.5.4.400] [PMID: 1423218]
[http://dx.doi.org/10.1002/immu.200390009] [PMID: 12594834]
[http://dx.doi.org/10.1016/S0008-6363(03)00361-4] [PMID: 14522411]
[http://dx.doi.org/10.4269/ajtmh.1993.48.637] [PMID: 8517482]
[PMID: 1541517]
[http://dx.doi.org/10.1038/356338a0] [PMID: 1549177]
[PMID: 8168945]
[PMID: 2104903]
[http://dx.doi.org/10.1046/j.1365-2249.2001.01478.x] [PMID: 11298135]
[http://dx.doi.org/10.1046/j.1440-1711.2002.01081.x] [PMID: 12067411]
[http://dx.doi.org/10.1016/j.peptides.2007.06.017] [PMID: 17683828]
[http://dx.doi.org/10.1016/S0161-5890(01)00059-1] [PMID: 11566321]
[http://dx.doi.org/10.1371/journal.pntd.0001294] [PMID: 21886854]
[http://dx.doi.org/10.4049/jimmunol.166.7.4596] [PMID: 11254717]
[http://dx.doi.org/10.1086/381682] [PMID: 14976609]
[http://dx.doi.org/10.1128/IAI.71.3.1185-1193.2003] [PMID: 12595431]
[http://dx.doi.org/10.4049/jimmunol.1500459] [PMID: 26385520]
[http://dx.doi.org/10.1371/journal.pntd.0003432] [PMID: 25569149]
[http://dx.doi.org/10.1371/journal.pone.0150996] [PMID: 26974162]
[http://dx.doi.org/10.1371/journal.pntd.0000512] [PMID: 19742301]
[http://dx.doi.org/10.1038/ni.2035] [PMID: 21739672]
[http://dx.doi.org/10.1002/eji.201343751] [PMID: 24258910]
[http://dx.doi.org/10.1038/nm.2446] [PMID: 21926977]
[http://dx.doi.org/10.21037/atm.2016.05.38] [PMID: 27386495]
[http://dx.doi.org/10.1172/JCI66327] [PMID: 23281401]
[http://dx.doi.org/10.1128/JVI.01948-14] [PMID: 25253339]
[http://dx.doi.org/10.1038/nm.4241] [PMID: 28060797]
[http://dx.doi.org/10.1038/nm0402-379] [PMID: 11927944]
[http://dx.doi.org/10.1002/cyto.a.20643] [PMID: 18785267]
[http://dx.doi.org/10.1002/eji.200526122] [PMID: 16106370]
[http://dx.doi.org/10.1038/ni889] [PMID: 12563257]
[http://dx.doi.org/10.1111/j.1365-3024.2009.01125.x] [PMID: 19646207]
[http://dx.doi.org/10.1371/journal.ppat.1003504] [PMID: 23874205]
[http://dx.doi.org/10.1371/journal.ppat.1002645] [PMID: 22532799]
[http://dx.doi.org/10.1371/journal.pntd.0000288] [PMID: 18846233]
[http://dx.doi.org/10.1371/journal.pntd.0002038] [PMID: 23383358]
[http://dx.doi.org/10.1038/nri1416] [PMID: 15286731]
[http://dx.doi.org/10.1038/nri2274] [PMID: 18323851]
[http://dx.doi.org/10.1182/blood-2005-12-4818] [PMID: 16467198]
[http://dx.doi.org/10.1038/nm.f.1774] [PMID: 18535580]
[http://dx.doi.org/10.1128/IAI.01459-08] [PMID: 19651871]
[http://dx.doi.org/10.1089/hum.2013.218] [PMID: 24568548]
[http://dx.doi.org/10.1128/IAI.01190-10] [PMID: 21357719]
[http://dx.doi.org/10.1371/journal.pntd.0002575] [PMID: 24349591]
[http://dx.doi.org/10.1186/1471-2334-12-198] [PMID: 22920436]
[http://dx.doi.org/10.1371/journal.ppat.1000947] [PMID: 20548953]
[http://dx.doi.org/10.1038/ni.1679] [PMID: 19043418]
[http://dx.doi.org/10.1016/j.pt.2012.07.001] [PMID: 22832368]
[http://dx.doi.org/10.4049/jimmunol.1202438] [PMID: 23264654]
[http://dx.doi.org/10.1371/journal.ppat.1000313] [PMID: 19247441]
[http://dx.doi.org/10.1038/nature04444] [PMID: 16382236]
[http://dx.doi.org/10.1038/ni.2180] [PMID: 22157630]
[http://dx.doi.org/10.1073/pnas.1009731107] [PMID: 20679213]
[http://dx.doi.org/10.1128/IAI.01047-10] [PMID: 21357717]
[http://dx.doi.org/10.4049/jimmunol.172.8.4893] [PMID: 15067068]
[http://dx.doi.org/10.4049/jimmunol.1602095] [PMID: 28258194]
[http://dx.doi.org/10.1093/jac/dks390] [PMID: 23104493]
[http://dx.doi.org/10.1186/1471-2334-12-123] [PMID: 22625224]
[http://dx.doi.org/10.1111/j.1365-3083.2006.01843.x] [PMID: 17032249]
[http://dx.doi.org/10.1645/GE-77R] [PMID: 14533683]
[http://dx.doi.org/10.1128/AAC.00779-08] [PMID: 19001113]
[http://dx.doi.org/10.1086/342510] [PMID: 12198628]
[http://dx.doi.org/10.1371/journal.pntd.0001277] [PMID: 21912712]
[http://dx.doi.org/10.1371/journal.pntd.0002989] [PMID: 25144227]
[http://dx.doi.org/10.1371/journal.pone.0065820] [PMID: 23776551]
[PMID: 10962268]
[http://dx.doi.org/10.1038/nature01441] [PMID: 12594515]
[http://dx.doi.org/10.1016/j.immuni.2012.05.015] [PMID: 22727490]
[http://dx.doi.org/10.4049/jimmunol.0900852] [PMID: 19692645]
[http://dx.doi.org/10.1016/S0165-2478(00)00205-4] [PMID: 10963810]
[http://dx.doi.org/10.1371/journal.pone.0035966] [PMID: 22574131]
[http://dx.doi.org/10.1186/s12879-016-1523-1] [PMID: 27138039]
[http://dx.doi.org/10.1146/annurev.immunol.021908.132723] [PMID: 19302048]
[http://dx.doi.org/10.1371/journal.pntd.0000992] [PMID: 21655351]
[http://dx.doi.org/10.1016/j.humimm.2008.10.015] [PMID: 19022313]
[http://dx.doi.org/10.1111/j.1365-3083.2005.01668.x] [PMID: 16179017]
[http://dx.doi.org/10.1111/j.1365-2249.2006.03123.x] [PMID: 16792677]
[http://dx.doi.org/10.3389/fimmu.2016.00093] [PMID: 27014272]
[http://dx.doi.org/10.1111/j.1365-3083.2012.02730.x] [PMID: 22670682]
[http://dx.doi.org/10.1086/648072] [PMID: 19877967]
[http://dx.doi.org/10.1371/journal.pntd.0004657] [PMID: 27128444]
[http://dx.doi.org/10.1093/intimm/dxm149] [PMID: 18195050]
[http://dx.doi.org/10.1111/j.1365-3024.2012.01378.x] [PMID: 22738032]
[http://dx.doi.org/10.1371/journal.pntd.0001630] [PMID: 22545173]
[http://dx.doi.org/10.1093/infdis/jis724] [PMID: 23204182]
[http://dx.doi.org/10.1111/j.1749-6632.2012.06627.x] [PMID: 22823432]
[http://dx.doi.org/10.1002/jmv.23289] [PMID: 22499005]
[http://dx.doi.org/10.1182/blood-2003-12-4395] [PMID: 15044252]
[http://dx.doi.org/10.1038/s41598-017-11926-2] [PMID: 28912605]
[http://dx.doi.org/10.1016/j.cellimm.2009.06.011] [PMID: 19616200]
[http://dx.doi.org/10.1371/journal.pntd.0006480] [PMID: 29750791]
[http://dx.doi.org/10.1016/j.virol.2014.12.033] [PMID: 25620767]
[http://dx.doi.org/10.1097/QCO.0000000000000478] [PMID: 30095485]
[http://dx.doi.org/10.1086/605091] [PMID: 19640226]
[http://dx.doi.org/10.1111/1471-0528.12396] [PMID: 23924273]
[http://dx.doi.org/10.1155/2014/401864] [PMID: 24949443]
[http://dx.doi.org/10.1016/j.actatropica.2015.07.016] [PMID: 26293886]
[http://dx.doi.org/10.1586/eri.10.74] [PMID: 20695749]
[http://dx.doi.org/10.1016/j.imlet.2014.06.013] [PMID: 24996040]
[http://dx.doi.org/10.1006/smim.2001.0316] [PMID: 11437629]
[http://dx.doi.org/10.1016/j.placenta.2015.07.124] [PMID: 26278059]
[http://dx.doi.org/10.4269/ajtmh.2010.10-0326] [PMID: 21036835]
[http://dx.doi.org/10.4269/ajtmh.2011.10-0015] [PMID: 21460012]
[http://dx.doi.org/10.1371/journal.pntd.0005627] [PMID: 28598971]
[http://dx.doi.org/10.1016/j.jri.2005.08.003] [PMID: 16236361]
[http://dx.doi.org/10.1016/j.jri.2008.12.001] [PMID: 19368976]
[http://dx.doi.org/10.1084/jem.20050019] [PMID: 16027236]
[http://dx.doi.org/10.1002/eji.200324632] [PMID: 15484187]
[http://dx.doi.org/10.1111/j.1600-0897.2009.00737.x] [PMID: 19811462]
[http://dx.doi.org/10.1086/382511] [PMID: 15031797]
[http://dx.doi.org/10.4269/ajtmh.2008.78.499] [PMID: 18337349]
[http://dx.doi.org/10.1016/j.actatropica.2003.09.020] [PMID: 14739025]
[http://dx.doi.org/10.1016/0002-9378(86)90092-X] [PMID: 3728579]
[http://dx.doi.org/10.1016/j.it.2014.07.010] [PMID: 25172617]
[http://dx.doi.org/10.1111/j.1365-3156.2006.01623.x] [PMID: 16640615]
[http://dx.doi.org/10.4269/ajtmh.2004.70.201] [PMID: 14993634]
[http://dx.doi.org/10.1371/journal.pone.0105017] [PMID: 25153531]
[http://dx.doi.org/10.1371/journal.pntd.0003312] [PMID: 25411847]
[http://dx.doi.org/10.1590/S0037-86822009000500002] [PMID: 19967227]
[http://dx.doi.org/10.1093/infdis/jix087] [PMID: 28201741]
[http://dx.doi.org/10.1590/0074-02760140347] [PMID: 25993401]