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The current vaccine against tuberculosis, live attenuated Mycobacterium bovis BCG, has variable efficacy, but development of an effective alternative is severely hampered by the lack of an immune correlate of protection. There has been a recent resurgence of interest in functional in vitro mycobacterial growth inhibition assays (MGIAs), which provide a measure of a range of different immune mechanisms and their interactions. We identified a positive correlation between mean corpuscular haemoglobin and in vitro growth of BCG in whole blood from healthy UK human volunteers. Mycobacterial growth in peripheral blood mononuclear cells (PBMC) from both humans and macaques was increased following the experimental addition of haemoglobin (Hb) or ferric iron, and reduced following addition of the iron chelator deferoxamine (DFO). Expression of Hb genes correlated positively with mycobacterial growth in whole blood from UK/Asian adults and, to a lesser extent, in PBMC from South African infants. Taken together our data indicate an association between Hb/iron levels and BCG growth in vitro, which may in part explain differences in findings between whole blood and PBMC MGIAs and should be considered when using such assays.

Original publication

DOI

10.1038/srep43478

Type

Journal article

Journal

Sci Rep

Publication Date

03/03/2017

Volume

7

Keywords

Adolescent, Adult, Animals, BCG Vaccine, Deferoxamine, Erythrocyte Indices, Gene Expression, Hemoglobins, Humans, Infant, Iron, Iron Chelating Agents, Leukocytes, Mononuclear, Lymphocyte Activation, Macaca mulatta, Microbial Sensitivity Tests, Middle Aged, Mycobacterium bovis, Mycobacterium tuberculosis, Primary Cell Culture, Vaccination