A Transcriptomic Network Identified in Uninfected Macrophages Responding to Inflammation Controls Intracellular Pathogen Survival
Lynette Beattie, Micely d'El-Rei Hermida, John WJ Moore, Asher Maroof, Najmeeyah Brown, Dimitris Lagos, Paul M Kaye
Cell Host & Microbe | CELL PRESS | Published : 2013
Intracellular pathogens modulate host cell function to promote their survival. However, in vitro infection studies do not account for the impact of host-derived inflammatory signals. Examining the response of liver-resident macrophages (Kupffer cells) in mice infected with the parasite Leishmania donovani, we identified a transcriptomic network operating in uninfected Kupffer cells exposed to inflammation but absent from Kupffer cells from the same animal that contained intracellular Leishmania. To test the hypothesis that regulated expression of genes within this transcriptomic network might impact parasite survival, we pharmacologically perturbed the activity of retinoid X receptor alpha (..View full abstract
Awarded by UK Medical Research Council
Awarded by Medical Research Council
This work was supported by a grant to P. M. K. from the UK Medical Research Council (G1000230). We wish to thank the staff of the Biological Services Facility and P. O'Toole, K. Hodgkinson, K. Hogg, G. Park, J. Marrison, N. Aziz, and C. Whalley (Technology Facility, University of York) for technical assistance. We also thank I. Graham and D. F. Smith for critical comments on the manuscript. The authors have no financial conflict of interest.