Utilize este identificador para referenciar este registo:
https://hdl.handle.net/10216/69106
Autor(es): | Sandro Silva Gomes Rui Appelberg Rasmus Larsen Miguel Parreira Soares Maria Salome Gomes |
Título: | Heme Catabolism by Heme Oxygenase-1 Confers Host Resistance to Mycobacterium Infection |
Data de publicação: | 2013 |
Resumo: | Heme oxygenases (HO) catalyze the rate-limiting step of heme degradation. The cytoprotective action of the inducible HO-1 isoform, encoded by the Hmox1 gene, is required for host protection against systemic infections. Here we report that upregulation of HO-1 expression in macrophages (M phi) is strictly required for protection against mycobacterial infection in mice. HO-1-deficient (Hmox1(-/-)) mice are more susceptible to intravenous Mycobacterium avium infection, failing to mount a protective granulomatous response and developing higher pathogen loads, than infected wild-type (Hmox1(+/+)) controls. Furthermore, Hmox1(-/-) mice also develop higher pathogen loads and ultimately succumb when challenged with a low-dose aerosol infection with Mycobacterium tuberculosis. The protective effect of HO-1 acts independently of adaptive immunity, as revealed in M. avium-infected Hmox1(-/-) versus Hmox1(+/+) SCID mice lacking mature B and T cells. In the absence of HO-1, heme accumulation acts as a cytotoxic pro-oxidant in infected M phi, an effect mimicked by exogenous heme administration to M. avium-infected wild-type M phi in vitro or to mice in vivo. In conclusion, HO-1 prevents the cytotoxic effect of heme in M phi, contributing critically to host resistance to Mycobacterium infection. |
Assunto: | Infecções, Medicina básica Infections, Basic medicine |
Áreas do conhecimento: | Ciências médicas e da saúde::Medicina básica Medical and Health sciences::Basic medicine |
URI: | https://hdl.handle.net/10216/69106 |
Tipo de Documento: | Artigo em Revista Científica Internacional |
Condições de Acesso: | openAccess |
Licença: | https://creativecommons.org/licenses/by-nc/4.0/ |
Aparece nas coleções: | ICBAS - Artigo em Revista Científica Internacional |
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