Abstract
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-1beta, 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-1beta secretion.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / metabolism
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Adenosine Triphosphate / physiology
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Animals
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Cell Line, Tumor
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Cervix Uteri / immunology
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Cervix Uteri / metabolism*
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Cervix Uteri / microbiology
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Chlamydia Infections / genetics
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Chlamydia Infections / immunology
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Chlamydia Infections / pathology*
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Chlamydia Infections / prevention & control*
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Chlamydia muridarum / growth & development
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Chlamydia muridarum / immunology
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Chronic Disease
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Epithelial Cells / immunology
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Epithelial Cells / metabolism
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Epithelial Cells / microbiology
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Fallopian Tubes / metabolism
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Fallopian Tubes / pathology
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Female
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Genital Diseases, Female / immunology
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Genital Diseases, Female / metabolism
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Genital Diseases, Female / microbiology
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Genital Diseases, Female / pathology
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Genital Diseases, Female / prevention & control*
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HeLa Cells
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Humans
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Interleukin-1beta / antagonists & inhibitors
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Interleukin-1beta / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Inbred DBA
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Mice, Knockout
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Purinergic P2 Receptor Agonists
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RNA, Messenger / biosynthesis
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Receptors, Purinergic P2 / deficiency
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Receptors, Purinergic P2 / metabolism
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Receptors, Purinergic P2 / physiology*
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Receptors, Purinergic P2X7
Substances
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Interleukin-1beta
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P2RX7 protein, human
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P2rx7 protein, mouse
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Purinergic P2 Receptor Agonists
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RNA, Messenger
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Receptors, Purinergic P2
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Receptors, Purinergic P2X7
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Adenosine Triphosphate