Experimental Therapy of Paracoccidioidomycosis Using P10-Primed Monocyte-Derived Dendritic Cells Isolated From Infected Mice

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Citações na Scopus
11
Tipo de produção
article
Data de publicação
2019
Título da Revista
ISSN da Revista
Título do Volume
Editora
FRONTIERS MEDIA SA
Autores
TAIRA, Cleison L.
DIAS, Lucas S.
SOUZA, Ana C. O.
NOSANCHUK, Joshua D.
TRAVASSOS, Luiz R.
Citação
FRONTIERS IN MICROBIOLOGY, v.10, article ID 1727, 12p, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Paracoccidioidomycosis (PCM) is an endemic mycosis in Latin American caused by the thermodimorphic fungi of the genus Paracoccidioides spp. Notably, a Th1 immune response is required to control PCM. In this context, dendritic cells (DCs) seem to be essential players in capture, processing and presentation of Paracoccidioides antigens to naive T cells and their further activation. We have previously demonstrated that differentiated DCs from bone marrow cells, pulsed with the immunoprotective peptide 10 (P10), effectively control experimental PCM immunocompetent and immunosuppressed mice. However, this procedure may not be infeasible or it is limited for the therapy of human patients. Therefore, we have sought a less invasive but equally effective approach that would better mimics the autologous transplant of DC in a human patient. Here, we isolated and generated monocyte differentiated dendritic cells (MoDCs) from infected mice, pulsed them with P-10, and used them in the therapy of PCM in syngeneic mice. Similar to the results using BMDCs, the P10-pulsed MoDCs stimulated the proliferation of CD4(+) T lymphocytes, induced a mixed production of Th-1/Th-2 cytokines and decreased the fungal burden in murine lungs in the setting of PCM. The process of differentiating MoDCs derived from an infected host, and subsequently used for therapy of PCM is much simpler than that for obtaining BMDCs, and represents a more reasonable approach to treat patients infected with Paracoccidioides. The results presented suggest that P10-primed MoDC may be a promising strategy to combat complicated PCM as well as to significantly shorten the lengthy requirements for treatment of patients with this fungal disease.
Palavras-chave
paracoccidioidomycosis, dendritic cells, peptide P10, vaccine, monocyte-derived dendritic cells
Referências
  1. Austyn JM, 2000, AM J RESP CRIT CARE, V162, pS146, DOI 10.1164/ajrccm.162.supplement_3.15tac1a
  2. Banchereau J, 1998, NATURE, V392, P245, DOI 10.1038/32588
  3. Bellocchio S, 2004, J IMMUNOL, V172, P3059, DOI 10.4049/jimmunol.172.5.3059
  4. Benard G, 2012, MED MYCOL, V50, P641, DOI 10.3109/13693786.2011.654135
  5. Brasel K, 2000, BLOOD, V96, P3029
  6. de Castro LF, 2013, J INFECTION, V67, P470, DOI 10.1016/j.jinf.2013.07.019
  7. Fonteneau JF, 2003, BLOOD, V101, P3520, DOI 10.1182/blood-2002-10-3063
  8. Heufler C, 1996, EUR J IMMUNOL, V26, P659, DOI 10.1002/eji.1830260323
  9. INABA K, 1992, J EXP MED, V176, P1693, DOI 10.1084/jem.176.6.1693
  10. Janeway CA, 2002, ANNU REV IMMUNOL, V20, P197, DOI 10.1146/annurev.immunol.20.083001.084359
  11. Magalhaes A, 2012, CLIN VACCINE IMMUNOL, V19, P23, DOI 10.1128/CVI.05414-11
  12. Martin-Fontecha A, 2003, J EXP MED, V198, P615, DOI 10.1084/jem.20030448
  13. Martinez R, 2017, J FUNGI, V3, DOI 10.3390/jof3010001
  14. Mildner A, 2013, ADV IMMUNOL, V120, P69, DOI 10.1016/B978-0-12-417028-5.00003-X
  15. MOSCARDIBACCHI M, 1994, J MED MICROBIOL, V40, P159, DOI 10.1099/00222615-40-3-159
  16. Netea MG, 2006, CLIN MICROBIOL INFEC, V12, P404, DOI 10.1111/j.1469-0691.2006.01388.x
  17. Plantinga M, 2013, IMMUNITY, V38, P322, DOI 10.1016/j.immuni.2012.10.016
  18. Prado M, 2009, MEM I OSWALDO CRUZ, V104, P513, DOI 10.1590/S0074-02762009000300019
  19. Robinson MJ, 2009, J EXP MED, V206, P2037, DOI 10.1084/jem.20082818
  20. Romani L, 2004, BLOOD, V103, P4232, DOI 10.1182/blood-2003-11-4036
  21. Romani L, 2011, NAT REV IMMUNOL, V11, P275, DOI 10.1038/nri2939
  22. Segura E, 2013, TRENDS IMMUNOL, V34, P440, DOI 10.1016/j.it.2013.06.001
  23. Serbina NV, 2003, IMMUNITY, V19, P59, DOI 10.1016/S1074-7613(03)00171-7
  24. Shikanai-Yasuda MA, 2006, REV SOC BRAS MED TRO, V39, P297, DOI 10.1590/S0037-86822006000300017
  25. Shortman K, 2002, NAT REV IMMUNOL, V2, P151, DOI 10.1038/nri746
  26. Shortman K, 2007, NAT REV IMMUNOL, V7, P19, DOI 10.1038/nri1996
  27. Silva LBR, 2017, FRONT MICROBIOL, V8, DOI 10.3389/fmicb.2017.01057
  28. STEINMAN RM, 1978, P NATL ACAD SCI USA, V75, P5132, DOI 10.1073/pnas.75.10.5132
  29. Taborda CP, 2015, REV INST MED TROP SP, V57, P21, DOI 10.1590/S0036-46652015000700005
  30. Taborda CP, 1998, INFECT IMMUN, V66, P786
  31. Tamoutounour S, 2012, EUR J IMMUNOL, V42, P3150, DOI 10.1002/eji.201242847
  32. Thind SK, 2015, VIRULENCE, V6, P424, DOI 10.4161/21505594.2014.965586
  33. Travassos LR, 2008, MYCOPATHOLOGIA, V165, P341, DOI 10.1007/s11046-007-9056-1
  34. Travassos LR, 2012, HUM VACC IMMUNOTHER, V8, P1450, DOI 10.4161/hv.21283
  35. Vieira GD, 2014, REV SOC BRAS MED TRO, V47, P63, DOI 10.1590/0037-8682-0225-2013