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Author(s): Sandro Silva Gomes
Rui Appelberg
Rasmus Larsen
Miguel Parreira Soares
Maria Salome Gomes
Title: Heme Catabolism by Heme Oxygenase-1 Confers Host Resistance to Mycobacterium Infection
Issue Date: 2013
Abstract: 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.
Subject: Infecções, Medicina básica
Infections, Basic medicine
Scientific areas: Ciências médicas e da saúde::Medicina básica
Medical and Health sciences::Basic medicine
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
Appears in Collections:ICBAS - Artigo em Revista Científica Internacional

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