title: The expression of ferritin, lactoferrin, transferrin receptor and solute carrier family 11A1 in the host response to BCG-vaccination and Mycobacterium tuberculosis challenge.
abstract: Iron is an essential cofactor for both mycobacterial growth during infection and for a successful protective immune response by the host. The immune response partly depends on the regulation of iron by the host, including the tight control of expression of the iron-storage protein, ferritin. BCG vaccination can protect against disease following Mycobacterium tuberculosis infection, but the mechanisms of protection remain unclear. To further explore these mechanisms, splenocytes from BCG-vaccinated guinea pigs were stimulated ex vivo with purified protein derivative from M. tuberculosis and a significant down-regulation of ferritin light- and heavy-chain was measured by reverse-transcription quantitative-PCR (P≤0.05 and ≤0.01, respectively). The mechanisms of this down-regulation were shown to involve TNFα and nitric oxide. A more in depth analysis of the mRNA expression profiles, including genes involved in iron metabolism, was performed using a guinea pig specific immunological microarray following ex vivo infection with M. tuberculosis of splenocytes from BCG-vaccinated and naïve guinea pigs. M. tuberculosis infection induced a pro-inflammatory response in splenocytes from both groups, resulting in down-regulation of ferritin (P≤0.05). In addition, lactoferrin (P≤0.002), transferrin receptor (P≤0.05) and solute carrier family 11A1 (P≤0.05), were only significantly down-regulated after infection of the splenocytes from BCG-vaccinated animals. The results show that expression of iron-metabolism genes is tightly regulated as part of the host response to M. tuberculosis infection and that BCG-vaccination enhances the ability of the host to mount an iron-restriction response which may in turn help to combat invasion by mycobacteria.
authors.affiliation: Microbiological Services, HPA Porton Down, Salisbury SP4 0JG, UK. ruth.thom@hpa.org.uk
authors.forename: R E
authors.initials: RE
authors.lastname: Thom
authors.forename: M J
authors.initials: MJ
authors.lastname: Elmore
authors.forename: A
authors.initials: A
authors.lastname: Williams
authors.forename: S C
authors.initials: SC
authors.lastname: Andrews
authors.forename: F
authors.initials: F
authors.lastname: Drobniewski
authors.forename: P D
authors.initials: PD
authors.lastname: Marsh
authors.forename: J A
authors.initials: JA
authors.lastname: Tree
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000276:immunology*; D027682:Cation Transport Proteins / Q000096:biosynthesis*; D005293:Ferritins / Q000096:biosynthesis*; D020869:Gene Expression Profiling; D006168:Guinea Pigs; D007501:Iron / Q000378:metabolism; D007781:Lactoferrin / Q000096:biosynthesis*; D046228:Microarray Analysis; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D011990:Receptors, Transferrin / Q000096:biosynthesis*; D014376:Tuberculosis / Q000517:prevention & control*; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D001500:BCG Vaccine; D027682:Cation Transport Proteins; D005293:Ferritins; D007501:Iron; D007781:Lactoferrin; D011990:Receptors, Transferrin; D000099173:Natural Resistance-associated Macrophage Protein 1