Parasite DNA and Markers of Decreased Immune Activation Associate Prospectively with Cardiac Functional Decline over 10 Years among <i>Trypanosoma cruzi</i> Seropositive Individuals in Brazil

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Tipo de produção
article
Data de publicação
2024
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Editora
MDPI
Autores
SUNDERRAJ, Ashwin
CUNHA, Luisa Marin
AVILA, Matheus
ALEXANDRIA, Shaina
FERREIRA, Ariela Mota
RIBEIRO, Antonio L. P.
NUNES, Maria do Carmo Pereira
LANDAY, Alan
Citação
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.25, n.1, article ID 44, 9p, 2024
Projetos de Pesquisa
Unidades Organizacionais
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Resumo
Parasitemia and inflammatory markers are cross-sectionally associated with chronic Chagas cardiomyopathy (CCC) among patients with Trypanosoma cruzi. However, the prospective association of the parasite load and host immune response-related characteristics with CCC (that is, progressors) among T. cruzi seropositive individuals has only been partially defined. In a cohort of T. cruzi seropositive patients in Montes Claros and Sao Paulo, Brazil who were followed over 10 years, we identified the association of a baseline T. cruzi parasite load and systemic markers of inflammation with a decline in cardiac function and/or the presence of cardiac congestion 10 years later. The progressors (n = 21) were individuals with a significant decline in the left ventricular ejection fraction and/or elevated markers of cardiac congestion after 10 years. The controls (n = 31) had normal markers of cardiac function and congestion at the baseline and at the follow-up. They were matched with the progressors on age, sex, and genetic ancestry. The progressors had higher mean parasite loads at the baseline than the controls (18.3 vs. 0.605 DNA parasite equivalents/20 mL, p < 0.05). Of the 384 inflammation-related proteins analyzed, 47 differed significantly at a false discovery rate- (FDR-) corrected p < 0.05 between the groups. There were 44 of these 47 proteins that were significantly higher in the controls compared to in the progressors, including the immune activation markers CCL21, CXCL12, and HCLS1 and several of the tumor necrosis factor superfamily of proteins. Among the individuals who were seropositive for T. cruzi at the baseline and who were followed over 10 years, those with incident CCC at the 10-year marker had a comparatively higher baseline of T. cruzi parasitemia and lower baseline markers of immune activation and chemotaxis. These findings generate the hypothesis that the early impairment of pathogen-killing immune responses predisposes individuals to CCC, which merits further study.
Palavras-chave
Chagas disease, infection, immune response, heart failure, Trypanosoma cruzi
Referências
  1. Abel LCJ, 2001, J AUTOIMMUN, V17, P99, DOI 10.1006/jaut.2001.0523
  2. Barinov A, 2017, P NATL ACAD SCI USA, V114, P2319, DOI 10.1073/pnas.1611958114
  3. Berbert LR, 2021, FRONT CELL INFECT MI, V11, DOI 10.3389/fcimb.2021.713150
  4. Castro-Ochoa KF, 2019, J LEUKOCYTE BIOL, V105, P881, DOI 10.1002/JLB.MR0618-212R
  5. CETRON MS, 1993, AM J TROP MED HYG, V49, P370, DOI 10.4269/ajtmh.1993.49.370
  6. de Oliveira MT, 2021, FRONT CARDIOVASC MED, V8, DOI 10.3389/fcvm.2021.741347
  7. Deng XT, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0079629
  8. Frade AF, 2013, BMC INFECT DIS, V13, DOI 10.1186/1471-2334-13-587
  9. Garnica MR, 2005, IMMUNOLOGY, V115, P399, DOI 10.1111/j.1365-2567.2005.02178.x
  10. Gomes JAS, 2003, INFECT IMMUN, V71, P1185, DOI 10.1128/IAI.71.3.1185-1193.2003
  11. Graefe SEB, 2003, MICROBES INFECT, V5, P833, DOI 10.1016/S1286-4579(03)00176-X
  12. Hölscher C, 1998, INFECT IMMUN, V66, P1208
  13. Johansen FE, 2000, SCAND J IMMUNOL, V52, P240
  14. Keating SM, 2015, INT J CARDIOL, V199, P451, DOI 10.1016/j.ijcard.2015.07.040
  15. KIERSZENBAUM F, 1982, J IMMUNOL, V129, P2202
  16. Lee YH, 2019, FRONT IMMUNOL, V10, DOI 10.3389/fimmu.2019.01172
  17. Nagasawa T, 2014, J MOL MED, V92, P433, DOI 10.1007/s00109-014-1123-8
  18. Nanatsue K, 2014, J HUM GENET, V59, P480, DOI 10.1038/jhg.2014.57
  19. Nogueira LG, 2012, PLOS NEGLECT TROP D, V6, DOI 10.1371/journal.pntd.0001867
  20. Noor S, 2010, INFECT IMMUN, V78, P2257, DOI 10.1128/IAI.01314-09
  21. Pérez-Antón E, 2021, PLOS NEGLECT TROP D, V15, DOI 10.1371/journal.pntd.0009059
  22. Pérez-Antón E, 2020, ACTA TROP, V202, DOI 10.1016/j.actatropica.2019.105242
  23. Pinho RT, 2016, FRONT IMMUNOL, V7, DOI 10.3389/fimmu.2016.00306
  24. Ferreira LRP, 2017, J INFECT DIS, V215, P387, DOI 10.1093/infdis/jiw540
  25. Ploix CC, 2011, BRAIN BEHAV IMMUN, V25, P883, DOI 10.1016/j.bbi.2010.09.014
  26. Rodrigues V, 2008, MICROBES INFECT, V10, P29, DOI 10.1016/j.micinf.2007.09.015
  27. Sabino EC, 2015, EUR J HEART FAIL, V17, P416, DOI 10.1002/ejhf.220
  28. Sabino EC, 2013, CIRCULATION, V127, P1105, DOI 10.1161/CIRCULATIONAHA.112.123612
  29. Saéz-Alquézar A, 1998, VOX SANG, V74, P228, DOI 10.1159/000030940
  30. Salles NA, 1996, TRANSFUSION, V36, P969, DOI 10.1046/j.1537-2995.1996.36111297091740.x
  31. Salvador F, 2020, AM J TROP MED HYG, V102, P159, DOI 10.4269/ajtmh.19-0550
  32. Sanders-van Wijk S, 2020, CIRCULATION, V142, P2029, DOI 10.1161/CIRCULATIONAHA.120.045810
  33. Santamaría MH, 2023, EXP PARASITOL, V248, DOI 10.1016/j.exppara.2023.108491
  34. TORRICO F, 1991, J IMMUNOL, V146, P3626
  35. Vitelli-Avelar DM, 2008, SCAND J IMMUNOL, V68, P516, DOI 10.1111/j.1365-3083.2008.02167.x
  36. Wu JH, 2021, BMC MED GENOMICS, V14, DOI 10.1186/s12920-021-01134-3