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

• Type: Article in International Scientific Journal
• Date: 2013

Authors

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

Journal

Title: Infection and Immunity

Vol. 81

Pages: 2536-2545

ISSN: 0019-9567

Publisher: American Society for Microbiology

Indexing

ISI Web of Knowledge - 42 Citations

Scopus - 55 Citations

Pubmed / Medline

Scientific classification

FOS: Medical and Health sciences > Basic medicine

CORDIS: Health sciences > Medical sciences > Medicine > Infections

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10