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Article
Reversible inhibition of Chlamydia trachomatis infection in epithelial cells due to stimulation of P2X4 receptors
Infection and Immunity
  • Matthew A. Pettengill, University of California, Merced
  • Camila Marques-da-Silva, University of California, Merced
  • Maria Luisa Avila, University of California, Merced
  • Verissa W. Lam, University of California, Merced
  • Ikechukwu Ollawa, University of California, Merced
  • Ali Abdul-Sater, University of California, Merced
  • Robson Coutinho-Silva, Federal University of Rio de Janeiro
  • Georg Hacker, University Medical Centre Freiburg
  • David M. Ojcius, University of California, Merced
  • Suellen d'Arc dos Santos Oliveira, Federal University of Rio de Janeiro
ORCiD
David M. Ojcius: 0000-0003-1461-4495
Document Type
Article
DOI
10.1128/IAI.00441-12
Publication Date
12-1-2012
Abstract

Bacterial infections of the mucosal epithelium are a major cause of human disease. The prolonged presence of microbial pathogens stimulates inflammation of the local tissues, which leads to changes in the molecular composition of the extracellular milieu. A well-characterized molecule that is released to the extracellular milieu by stressed or infected cells is extracellular ATP and its ecto-enzymatic degradation products, which function as signaling molecules through ligation of purinergic receptors. There has been little information, however, on the effects of the extracellular metabolites on bacterial growth in inflamed tissues. Millimolar concentrations of ATP have been previously shown to inhibit irreversibly bacterial infection through ligation of P2X7 receptors. We show here that the proinflammatory mediator, ATP, is released from Chlamydia trachomatis-infected epithelial cells. Moreover, further stimulation of the infected cells with micromolar extracellular ADP or ATP significantly impairs the growth of the bacteria, with a profile characteristic of the involvement of P2X4 receptors. A specific role for P2X4 was confirmed using cells overexpressing P2X4. The chlamydiae remain viable and return to normal growth kinetics after removal of the extracellular stimulus, similar to responses previously described for persistence of chlamydial infection.

Citation Information
Matthew A. Pettengill, Camila Marques-da-Silva, Maria Luisa Avila, Verissa W. Lam, et al.. "Reversible inhibition of Chlamydia trachomatis infection in epithelial cells due to stimulation of P2X4 receptors" Infection and Immunity Vol. 80 Iss. 12 (2012) p. 4232 - 4238 ISSN: 0019-9567
Available at: http://works.bepress.com/david-ojcius/204/