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* Division of Pediatric Infectious Diseases, Arkansas Children’s Hospital and University of Arkansas for Medical Sciences, Little Rock, AR 72202;
Université Paris-Denis Diderot, Paris, France;
School of Natural Sciences, University of California, Merced, CA 95344; and
Milstead Pathology PC, Atlanta, GA 30012
Ligation of the purinergic receptor, P2X7R, with its agonist ATP has been previously shown to inhibit intracellular infection by chlamydiae and mycobacteria in macrophages. The effect of P2X7R on chlamydial infection had never been investigated in the preferred target cells of chlamydiae, cervical epithelial cells, nor in vaginally infected mice. In this study, we show that treatment of epithelial cells with P2X7R agonists inhibits partially Chlamydia infection in epithelial cells. Chelation of ATP with magnesium or pretreatment with a P2X7R antagonist blocks the inhibitory effects of ATP. Similarly to previous results obtained with macrophages, ATP-mediated inhibition of infection in epithelial cells requires activation of host-cell phospholipase D. Vaginal infection was also more efficient in P2X7R-deficient mice, which also displayed a higher level of acute inflammation in the endocervix, oviduct, and mesosalpingeal tissues than in infected wild-type mice. However, secretion of IL-1
, which requires P2X7R ligation during infection by other pathogens, was decreased mildly and only at short times of infection. Taken together, these results suggest that P2X7R affects Chlamydia infection by directly inhibiting infection in epithelial cells, rather than through the ability of P2X7R to modulate IL-1 secretion.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grant R01 AI054624, Université Paris-Denis Diderot, and University of California.
2 Address correspondence and reprint requests to Dr. David M. Ojcius, School of Natural Sciences, P.O. Box 2039, University of California, Merced, CA 95344. E-mail address: dojcius{at}ucmerced.edu
3 Abbreviations used in this paper: PAMP, pathogen-associated molecular pattern; ATPe, extracellular ATP; BzATP, 3-O-(4-benzoylbenzoyl) ATP; IFU, inclusion-forming unit; oATP, oxidized ATP; PLD, phospholipase D.
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