The expression of ferritin, lactoferrin, transferrin receptor and solute carrier family 11A1 in the host response to BCG-vaccination and Mycobacterium tuberculosis challenge

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• 作者：R.E. Thom^a ; ^{ruth.thom@hpa.org.uk} ; M.J. Elmore^a ; A. Williams^a ; S.C. Andrews^b ; F. Drobniewski^c ; P.D. Marsh^a ; J.A. Tree^a
• 关键词：Tuberculosis ; Guinea pig ; BCG ; Iron ; Ferritin ; Biomarkers
• 刊名：Vaccine
• 出版年：2012
• 期刊代码：89_0264410x
• 类别：imm
• 出版时间：2 May, 2012
• 卷：30
• 期：21
• 页码：3159-3168
• 文件大小：922 K

摘要

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 鈮?#xA0;0.05 and 鈮?.01, respectively). The mechanisms of this down-regulation were shown to involve TNF伪 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 na茂ve guinea pigs. M. tuberculosis infection induced a pro-inflammatory response in splenocytes from both groups, resulting in down-regulation of ferritin (P 鈮?#xA0;0.05). In addition, lactoferrin (P 鈮?#xA0;0.002), transferrin receptor (P 鈮?#xA0;0.05) and solute carrier family 11A1 (P 鈮?#xA0;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.