University of Worcester Worcester Research and Publications
 
  USER PANEL:
  ABOUT THE COLLECTION:
  CONTACT DETAILS:

ATP-induced autophagy is associated with rapid killing of intracellular mycobacteria within human monocytes/macrophages

Biswas, D., Qureshi, O., Lee, W., Croudace, Joanne, Mura, M. and Lammas, D. (2008) ATP-induced autophagy is associated with rapid killing of intracellular mycobacteria within human monocytes/macrophages. BMC Immunology, 9 (35). pp. 1-10. ISSN Electronic: 1471-2172

[thumbnail of 1471-2172-9-35.pdf]
Preview
Text
1471-2172-9-35.pdf - Published Version
Available under License Creative Commons Attribution.

Download (1MB) | Preview

Abstract

Background

We have previously reported that ATP treatment of M bovis-BCG infected human macrophages induces P2X7 receptor-dependent killing of intracellular mycobacteria. The mechanism mediating this bactericidal effect has not been full characterized but is known to be Ca2+-dependent and to promote the maturation and acidification of mycobacteria-containing phagosomes. In this study we demonstrate that the ATP/P2X7-mediated, mycobactericidal effect also involves the induction of cell autophagy.

Results

We report that 3 mM ATP induces rapid cell autophagy in THP1 cells and monocyte-derived macrophages within 30 minutes post-treatment, as revealed by the expression of LC3-II bands on western blot analysis. Using Ca2+-free media and selective P2X7 agonists and antagonists, ATP-induced cell autophagy was shown to be Ca2+ and P2X7 receptor-dependent. Electron microscopy of ATP-treated, BCG-infected MDMs revealed the presence of the bacteria within characteristic double-membraned autophagosomes. Confocal analysis further confirmed that pharmacological inhibition of autophagy by wortmannin or pre-treatment of macrophages with anti-P2X7 antibody blocked ATP-induced phago-lysosomal fusion. Induction of cell autophagy with ATP was also temporally associated with a fall in intracellular mycobacterial viability, which was suppressed by treatment with wortmannin or the selective P2X7 antagonist, oxidized ATP (oATP).

Conclusion

We provide the first evidence that ATP/P2X7-mediated killing of intracellular mycobacteria involves the induction of cell autophagy. The findings support the hypothesis that autophagy plays a key role in the control of mycobacterial infections.

Item Type: Article
Uncontrolled Discrete Keywords: THP1 Cell, P2X7 Receptor, Cell Autophagy, Intracellular Mycobacterium, P2X7 Agonist
Divisions: College of Health, Life and Environmental Sciences > School of Science and the Environment
Related URLs:
Copyright Info: This is an Open Access article, Distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited., © 2008 Biswas et al; licensee BioMed Central Ltd
Depositing User: Joanne Whittaker
Date Deposited: 13 Mar 2024 14:11
Last Modified: 20 Mar 2024 13:16
URI: https://worc-9.eprints-hosting.org/id/eprint/13718

Actions (login required)

View Item View Item
 
     
Worcester Research and Publications is powered by EPrints 3 which is developed by the School of Electronics and Computer Science at the University of Southampton. More information and software credits.