Heme Catabolism by Heme Oxygenase-1 Confers Host Resistance to Mycobacterium Infection

• Tipo: Artigo em Revista Científica Internacional
• Data: 2013

Autores

Sandro Silva Gomes (Autor) Outra; Rui Appelberg (Autor) ICBAS; Rasmus Larsen (Autor) Outra; Miguel Parreira Soares (Autor) Outra; Maria Salome Gomes (Autor) ICBAS

Revista

Título: Infection and Immunity

Vol. 81

Páginas: 2536-2545

ISSN: 0019-9567

Editora: American Society for Microbiology

Indexação

ISI Web of Knowledge - 42 Citações

Scopus - 55 Citações

Pubmed / Medline

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina básica

CORDIS: Ciências da Saúde > Ciências Médicas > Medicina > Infecções

Outras Informações

ID Authenticus: P-00H-XSK

DOI: 10.1128/iai.00251-13

Abstract (EN): 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 10