Impact of selective immune-cell depletion on growth of Mycobacterium tuberculosis (Mtb) in a whole-blood bactericidal activity (WBA) assay

Gail B Cross; Benjamin C-M Yeo; Paul Edward Hutchinson; Mark C Tan; Rupangi Verma; Qingshu Lu; Nicholas I Paton

doi:10.1371/journal.pone.0216616

Impact of selective immune-cell depletion on growth of Mycobacterium tuberculosis (Mtb) in a whole-blood bactericidal activity (WBA) assay

PLoS One. 2019 May 17;14(5):e0216616. doi: 10.1371/journal.pone.0216616. eCollection 2019.

Authors

Gail B Cross^{1

2}, Benjamin C-M Yeo¹, Paul Edward Hutchinson³, Mark C Tan¹, Rupangi Verma¹, Qingshu Lu⁴, Nicholas I Paton^{1

2}

Affiliations

¹ Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
² Division of Infectious Diseases, University Medicine Cluster, National University Hospital, Singapore.
³ Flow Cytometry Lab, Life Sciences Institute, National University of Singapore, Singapore.
⁴ Singapore Clinical Research Institute, Singapore.

Abstract

We investigated the contribution of host immune cells to bacterial killing in a whole-blood bactericidal activity (WBA) assay, an ex vivo model used to test efficacy of drugs against mycobacterium tuberculosis (Mtb). We performed WBA assays with immuno-magnetic depletion of specific cell types, in the presence or absence of rifampicin. Innate immune cells decreased Mtb growth in absence of drug, but appeared to diminish the cidal activity of rifampicin, possibly attributable to intracellular bacterial sequestration. Adaptive immune cells had no effect with or without drug. The WBA assay may have potential for testing adjunctive host-directed therapies acting on phagocytic cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antitubercular Agents / pharmacology
Biological Assay / methods*
Blood Bactericidal Activity / drug effects
Blood Bactericidal Activity / immunology*
Humans
Mycobacterium tuberculosis / drug effects
Mycobacterium tuberculosis / growth & development*
Mycobacterium tuberculosis / immunology
Rifampin / pharmacology*
Tuberculosis / drug therapy
Tuberculosis / immunology
Tuberculosis / microbiology*

Substances

Antitubercular Agents
Rifampin

Grants and funding

This research was funded by Singapore Ministry of Health’s National Medical Research Council (NMRC), TCR Flagship grant, NMRC/TCR/011- NUHS/2014 to NIP; Center Grant ‘MINE’, Research Core #4, NMRC/CG/013/2013 to NIP; NLAM Clinician Scientist Unit “Pitch for Funds” research grant PFFR-23 September 2015 to GBC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.