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K. Shimazaki, A. M. Chan, M. Wadehra, J. Braun, K. A. Kelly, L. K. Gordon; Antibody Blockade of Epithelial Membrane Protein 2 (emp2) Abrogates Chlamydia Infectivity in the Murine Eye and Genital Tract. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4746.
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Epithelial Membrane Protein 2 (EMP2) is highly expressed in the eye, lung, and genitourinary tract, all sites of Chlamydia infection. Expression levels of EMP2 correlate with infectivity of Chlamydia in an in vitro system using multiple cell lines. In this present study, we investigated the effect of EMP2 blockade on chlamydial infectivity in vivo using anti-EMP2 antibodies in ocular and genital tract infection models.
BALB/c mice were used for infection models. For ocular infection, either 2.5 µg of control or anti-EMP2 antibody was placed in the upper fornix of the eye prior to Chlamydia muridarum (5 X 105 IFU/eye) infection. Chlamydial infectivity was detected in conjunctiva swabs performed at days 0, 3, and 6, and quantified by bacterial load (IFU) measurement and quantitative PCR (Q-PCR). For genital tract infection, pre-treatment with either 5 µg of control or anti-EMP2 antibody was performed prior to C. muridarum (1.5 X 105 IFU/mouse) infection. Chlamydial infectivity was detected at day 4 as described.
Blockade of the 2nd extracellular loop of EMP2 with the anti-EMP2 antibody caused decreased levels of bacterial burden in Chlamydia infected mice as compared to the controls. In the genital model, the control antibody diminished recovery of live C. muridarum, and this was concordant with Q-PCR data for genomic recovery. However, in comparison to these results, use of the specific anti-EMP2 antibody resulted in an additional 80% reduction in quantitative recovery of Chlamydia genome. In the ocular model, recovery of chlamydial genome suggested a similar reduction after treatment with the anti-EMP2 antibody. Additional experiments are needed to resolve the issue of whether EMP2 blocked infectivity in the eye as the recovery of the infectious organisms were below the detection limit.
Concordant with previous in vitro studies, chlamydial recovery was dramatically suppressed by blockade of the surface EMP2 in both ocular and genital tract animal infection models. This study provides additional evidence for the significance of EMP2 in pathogenesis of chlamydial infections. Additional studies that define the specific interactions between Chlamydia and EMP2 may reveal potential strategies for disease prevention.
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