Evidence for a link between iron metabolism and Nramp1 gene function in innate resistance against Mycobacterium avium

• Type: Article in International Scientific Journal
• Date: 1998

Authors

Gomes, MS (Author) Other; Appelberg, R (Author) ICBAS

Journal

Title: Immunology

Vol. 95

Pages: 165-168

ISSN: 0019-2805

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 71 Citations

Scopus - 82 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-00H-KBD

DOI: 10.1046/j.1365-2567.1998.00630.x

Abstract (EN): In the mouse, the progression of the Mycobacterium avium infection is highly dependent on the Nramp1 gene. Strains of mice that express the Nramp1(D169) allele are highly susceptible to M. avium infections, while Nramp1(G169) strains of mice can control them. Recently, the Nramp1 gene has been cloned and characterized as coding a transmembrane protein, probably involved in divalent cation transport. One possible function of this protein could be the transport of iron out of the parasite-harbouring phagosome. Previous work in our lab has shown both in vitro (in macrophage cultures) and in vivo, that the growth rate of M. avium is highly dependent on the amount of iron available in the system. To try to correlate this with the Nramp1 gene function, BALB/c (susceptible) and C.D2 (resistant) congenic mice were treated for 20 days with different doses of iron-dextran, so as to induce different degrees of iron overload, and infected with M. avium 2447. Iron administration increased M. avium growth in infected organs in a dose-dependent manner at the same time as it decreased the difference in mycobacterial growth between the two mouse strains. These results indicate that an excess of iron hampers Nramp1-encoded function, strongly suggesting a direct involvement of the Nramp1-encoded protein in the transport of this cation.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 4