| First Author | Silva-Gomes S | Year | 2013 |
| Journal | Infect Immun | Volume | 81 |
| Issue | 7 | Pages | 2536-45 |
| PubMed ID | 23630967 | Mgi Jnum | J:199723 |
| Mgi Id | MGI:5504546 | Doi | 10.1128/IAI.00251-13 |
| Citation | Silva-Gomes S, et al. (2013) Heme catabolism by heme oxygenase-1 confers host resistance to Mycobacterium infection. Infect Immun 81(7):2536-45 |
| abstractText | 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) 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, an effect mimicked by exogenous heme administration to M. avium-infected wild-type M in vitro or to mice in vivo. In conclusion, HO-1 prevents the cytotoxic effect of heme in M, contributing critically to host resistance to Mycobacterium infection. |
