Autor(es):
Oliveira, Martinha S. 
; Fraga, Alexandra G. ; Torrado, Egídio ; Castro, António G. ; Pereira, João P. ; Longatto Filho, Adhemar ; Milanezi, Fernanda ; Schmitt, Fernando C. ; Meyers, Wayne M. ; Portaels, Françoise ; Silva, Manuel T. ; Pedrosa, Jorge
Data: 2005
Identificador Persistente: http://hdl.handle.net/1822/3972
Origem: RepositóriUM - Universidade do Minho
Assunto(s): Infection; Mycobacterium ulcerans; Persistent inflammation; Mice
Descrição
Buruli ulcer (BU) is a devastating, necrotizing, tropical skin disease caused by infections with Mycobacterium
ulcerans. In contrast to other mycobacterioses, BU has been associated with minimal or absent inflammation.
However, here we show that in the mouse M. ulcerans induces persistent inflammatory responses with viru-lence-
dependent patterns. Mycolactone-positive, cytotoxic strains are virulent for mice and multiply progres-sively,
inducing both early and persistent acute inflammatory responses. The cytotoxicity of these strains leads
to progressive destruction of the inflammatory infiltrates by postapoptotic secondary necrosis, generating
necrotic acellular areas with extracellular bacilli released by the lysis of infected phagocytes. The necrotic
areas, always surrounded by acute inflammatory infiltrates, expand through the progressive invasion of healthy
tissues around the initial necrotic lesions by bacteria and by newly recruited acute inflammatory cells. Our
observations show that the lack of inflammatory infiltrates in the extensive areas of necrosis seen in advanced
infections results from the destruction of continuously produced inflammatory infiltrates and not from M.
ulcerans-induced local or systemic immunosuppression. Whether this is the mechanism behind the predomi-nance
of minimal or absent inflammatory responses in BU biopsies remains to be elucidated.
