Spontaneous Healing of Mycobacterium ulcerans Lesions in the Guinea Pig Model

Carregando...
Imagem de Miniatura
Citações na Scopus
15
Tipo de produção
article
Data de publicação
2015
Editora
PUBLIC LIBRARY SCIENCE
Indexadores
Título da Revista
ISSN da Revista
Título do Volume
Autores
SILVA-GOMES, Rita
MARCQ, Elly
TRIGO, Gabriela
GONCALVES, Carine M.
CASTRO, Antonio G.
PEDROSA, Jorge
FRAGA, Alexandra G.
Autor de Grupo de pesquisa
Editores
Coordenadores
Organizadores
Citação
PLOS NEGLECTED TROPICAL DISEASES, v.9, n.12, article ID e0004265, 12p, 2015
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Buruli Ulcer (BU) is a necrotizing skin disease caused by Mycobacterium ulcerans infection. BU is characterized by a wide range of clinical forms, including non-ulcerative cutaneous lesions that can evolve into severe ulcers if left untreated. Nevertheless, spontaneous healing has been reported to occur, although knowledge on this process is scarce both in naturally infected humans and experimental models of infection. Animal models are useful since they mimic different spectrums of human BU disease and have the potential to elucidate the pathogenic/protective pathway(s) involved in disease/healing. In this time-lapsed study, we characterized the guinea pig, an animal model of resistance to M. ulcerans, focusing on the macroscopic, microbiological and histological evolution throughout the entire experimental infectious process. Subcutaneous infection of guinea pigs with a virulent strain of M. ulcerans led to early localized swelling, which evolved into small well defined ulcers. These macroscopic observations correlated with the presence of necrosis, acute inflammatory infiltrate and an abundant bacterial load. By the end of the infectious process when ulcerative lesions healed, M. ulcerans viability decreased and the subcutaneous tissue organization returned to its normal state after a process of continuous healing characterized by tissue granulation and reepethelialization. In conclusion, we show that the experimental M. ulcerans infection of the guinea pig mimics the process of spontaneous healing described in BU patients, displaying the potential to uncover correlates of protection against BU, which can ultimately contribute to the development of new prophylactic and therapeutic strategies.
Palavras-chave
Referências
  1. George KM, 1999, SCIENCE, V283, P854, DOI 10.1126/science.283.5403.854
  2. KRIEG RE, 1974, ARCH DERMATOL, V110, P783, DOI 10.1001/archderm.110.5.783
  3. O'Brien C, 2013, AUST VET J, V91, P296, DOI 10.1111/avj.12071
  4. Tanghe A, 2007, INFECT IMMUN, V75, P2642, DOI 10.1128/IAI.01622-06
  5. Marsollier L, 2003, INT J ANTIMICROB AG, V22, P562, DOI 10.1016/S0924-8579(03)00240-1
  6. Torrado E, 2007, INFECT IMMUN, V75, P977, DOI 10.1128/IAI.00889-06
  7. Bentoucha A, 2001, ANTIMICROB AGENTS CH, V45, P3109, DOI 10.1128/AAC.45.11.3109-3112.2001
  8. READ JK, 1974, INFECT IMMUN, V9, P1114
  9. Coutanceau E, 2007, J EXP MED, V204, P1395, DOI 10.1084/jem.20070234
  10. REVILL WDL, 1973, LANCET, V2, P873
  11. Silva MT, 2009, LANCET INFECT DIS, V9, P699, DOI 10.1016/S1473-3099(09)70234-8
  12. Oliveira MS, 2005, INFECT IMMUN, V73, P6299, DOI 10.1128/IAI.73.10.6299-6310.2005
  13. Torrado E, 2007, INFECT IMMUN, V75, P3979, DOI 10.1128/IAI.00290-07
  14. Dega H, 2000, ANTIMICROB AGENTS CH, V44, P2367, DOI 10.1128/AAC.44.9.2367-2372.2000
  15. MACCALLUM P, 1948, J PATHOL BACTERIOL, V60, P93, DOI 10.1002/path.1700600111
  16. Dega H, 2002, ANTIMICROB AGENTS CH, V46, P3193, DOI 10.1128/AAC.46.10.3193-3196.2002
  17. Hong H, 2005, CHEMBIOCHEM, V6, P643, DOI 10.1002/cbic.200400339
  18. Fraga AG, 2011, INFECT IMMUN, V79, P421, DOI 10.1128/IAI.00820-10
  19. Walsh DS, 2008, T ROY SOC TROP MED H, V102, P969, DOI 10.1016/j.trstmh.2008.06.006
  20. Tanghe A, 2001, INFECT IMMUN, V69, P5403, DOI 10.1128/IAI.69.9.5403-5411.2001
  21. Ellen DE, 2003, TROP MED INT HEALTH, V8, P90, DOI 10.1046/j.1365-3156.2003.00976.x
  22. Coutanceau E, 2006, MICROBES INFECT, V8, P2075, DOI 10.1016/j.micinf.2006.03.009
  23. Huygen K, 2009, MED MICROBIOL IMMUN, V198, P69, DOI 10.1007/s00430-009-0109-6
  24. George KM, 2000, INFECT IMMUN, V68, P877, DOI 10.1128/IAI.68.2.877-883.2000
  25. Torrado E, 2010, J IMMUNOL, V184, P947, DOI 10.4049/jimmunol.0902717
  26. Bolz M, 2014, PLOS NEGLECT TROP D, V8, DOI 10.1371/journal.pntd.0002968
  27. Carson C, 2014, PLOS NEGLECT TROP D, V8, DOI 10.1371/journal.pntd.0002668
  28. Connor DH, 1966, ARCH PATH, V81, P17
  29. Fraga AG, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0033406
  30. Fyfe JAM, 2010, PLOS NEGLECT TROP D, V4, DOI 10.1371/journal.pntd.0000791
  31. Gama JB, 2014, PLOS NEGLECT TROP D, V8, DOI 10.1371/journal.pntd.0003066
  32. Gordon CL, 2011, PLOS NEGLECT TROP D, V5, DOI 10.1371/journal.pntd.0001290
  33. Lagarrigue V, 2000, Med Trop (Mars), V60, P262
  34. Martins TG, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0032740
  35. O'Brien CR, 2014, PLOS NEGLECT TROP D, V8, DOI 10.1371/journal.pntd.0002666
  36. Portaels F, 2003, B SEANC ACAD R SCI O, V49, P30
  37. Tanghe A, 2008, PLOS NEGLECT TROP D, V2, DOI 10.1371/journal.pntd.0000199
  38. Walsh DS, 2007, AM J TROP MED HYG, V76, P132
  39. World Health Organization, 2004, WHOCDSCPEGBUI200410