The influence of haemoglobin and iron on in vitro mycobacterial growth inhibition assays

Rachel Tanner*, Matthew K. O'Shea, Andrew D. White, Julius Müller, Rachel Harrington-Kandt, Magali Matsumiya, Michael Dennis, Eneida A. Parizotto, Stephanie Harris, Elena Stylianou, Vivek Naranbhai, Paulo Bettencourt, Hal Drakesmith, Sally Sharpe, Helen A. Fletcher, Helen McShane

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

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 languageEnglish
Article number43478
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 3 Mar 2017

Bibliographical note

Funding Information:
We are grateful to Aeras, UFAW (Universities Federation for Animal Welfare), EURIPRED (European Research Infrastructures for Poverty Related Diseases) and TBVAC2020 for grants supporting this work. HMcS is a Wellcome Trust Senior Clinical Research Fellow.

Publisher Copyright:
© The Author(s) 2017.

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