| First Author | Schaible UE | Year | 2002 |
| Journal | J Exp Med | Volume | 196 |
| Issue | 11 | Pages | 1507-13 |
| PubMed ID | 12461085 | Mgi Jnum | J:80527 |
| Mgi Id | MGI:2446012 | Doi | 10.1084/jem.20020897 |
| Citation | Schaible UE, et al. (2002) Correction of the Iron Overload Defect in beta-2-Microglobulin Knockout Mice by Lactoferrin Abolishes Their Increased Susceptibility to Tuberculosis. J Exp Med 196(11):1507-13 |
| abstractText | As a resident of early endosomal phagosomes, Mycobacterium tuberculosis is connected to the iron uptake system of the host macrophage. beta-2-microglobulin (beta2m) knockout (KO) mice are more susceptible to tuberculosis than wild-type mice, which is generally taken as a proof for the role of major histocompatibility complex class I (MHC-I)-restricted CD8 T cells in protection against M. tuberculosis. However, beta2m associates with a number of MHC-I-like proteins, including HFE. This protein regulates transferrin receptor mediated iron uptake and mutations in its gene cause hereditary iron overload (hemochromatosis). Accordingly, beta2m-deficient mice suffer from tissue iron overload. Here, we show that modulating the extracellular iron pool in beta2m-KO mice by lactoferrin treatment significantly reduces the burden of M. tuberculosis to numbers comparable to those observed in MHC class I-KO mice. In parallel, the generation of nitric oxide impaired in beta2m-KO mice was rescued. Conversely, iron overload in the immunocompetent host exacerbated disease. Consistent with this, iron deprivation in infected resting macrophages was detrimental for intracellular mycobacteria. Our data establish: (a) defective iron metabolism explains the increased susceptibility of beta2m-KO mice over MHC-I-KO mice, and (b) iron overload represents an exacerbating cofactor for tuberculosis. |
