Efficacy of an Immune Modulator in Experimental <i>Chlamydia trachomatis</i> Infection of the Female Genital Tract

Lyons, Joseph M.; Ito, James I.; Morré, Servaas A.

doi:https://doi.org/10.1155/IDOG/2006/61265

Infectious Diseases in Obstetrics and Gynecology

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Clinical Study | Open Access

Volume 2006 | Article ID 061265 | https://doi.org/10.1155/IDOG/2006/61265

Efficacy of an Immune Modulator in Experimental Chlamydia trachomatis Infection of the Female Genital Tract

Joseph M. Lyons,¹James I. Ito,¹and Servaas A. Morré²

Received08 Mar 2005

Revised31 Mar 2005

Accepted30 Apr 2005

Published07 Mar 2006

Abstract

Objective. The aim of this study was to determine if vaginal application of the immune response modifier imiquimod (Aldara cream, 3M Pharmaceuticals, St Paul, Minn) would alter the course and/or outcome of female genital tract infection with a human isolate of Chlamydia trachomatis in a murine model. Methods. Groups of CF-1 mice were treated with Aldara on three different schedules: (1) ongoing beginning 5 days prior to and continuing through day 5 of infection; (2) a single prophylactic dose 2 hours prior to infection; and (3) therapeutic from day 4 to day 14 of infection. Mice were infected vaginally with a serovar D strain of C trachomatis, and monitored by culture to determine the level of shedding and duration of infection. Results. We observed a significant reduction in both duration of infection and the level of shedding during the acute phase in mice treated on an ongoing basis commencing 5 days prior to infection. There was no effect with respect to the other regimens. Conclusion. These results demonstrate that ongoing Aldara treatment has efficacy and may enhance local innate immunity which reduces the duration of subsequent infection with human isolates of C trachomatis in a murine model of female genital tract infection.

References

R L Miller, J F Gerster, M L Owens, H B Slade, and M A Tomai, “Imiquimod applied topically: a novel immune response modifier and new class of drug,” International Journal of Immunopharmacology, vol. 21, no. 1, pp. 1–14, 1999.
View at: Google Scholar
S K Tyring, I Arany, M A Stanley et al., “A randomized, controlled, molecular study of condylomata acuminata clearance during treatment with imiquimod,” The Journal of Infectious Diseases, vol. 178, no. 2, pp. 551–555, 1998.
View at: Google Scholar
H Tran, G Moreno, and S Shumack, “Imiquimod as a dermatological therapy,” Expert Opinion on Pharmacotherapy, vol. 5, no. 2, pp. 427–438, 2004.
View at: Google Scholar
D I Bernstein and C J Harrison, “Effects of the immunomodulating agent R837 on acute and latent herpes simplex virus type 2 infections,” Antimicrobial Agents and Chemotherapy, vol. 33, no. 9, pp. 1511–1515, 1989.
View at: Google Scholar
S Buates and G Matlashewski, “Treatment of experimental leishmaniasis with the immunomodulators imiquimod and S-28463: efficacy and mode of action,” The Journal of Infectious Diseases, vol. 179, no. 6, pp. 1485–1494, 1999.
View at: Google Scholar
J Gilbert, M M Drehs, and J M Weinberg, “Topical imiquimod for acyclovir-unresponsive herpes simplex virus 2 infection,” Archives of Dermatology, vol. 137, no. 8, pp. 1015–1017, 2001.
View at: Google Scholar
T W Schacker, M Conant, C Thoming, T Stanczak, Z Wang, and M Smith, “Imiquimod 5-percent cream does not alter the natural history of recurrent herpes genitalis: a phase II, randomized, double-blind, placebo-controlled study,” Antimicrobial Agents and Chemotherapy, vol. 46, no. 10, pp. 3243–3248, 2002.
View at: Google Scholar
I Arevalo, B Ward, R L Miller et al., “Successful treatment of drug-resistant cutaneous leishmaniasis in humans by use of imiquimod, an immunomodulator,” Clinical Infectious Diseases, vol. 33, no. 11, pp. 1847–1851, 2001.
View at: Google Scholar
J Seeberger, S Daoud, and J Pammer, “Transient effect of topical treatment of cutaneous leishmaniasis with imiquimod,” International Journal of Dermatology, vol. 42, no. 7, pp. 576–579, 2003.
View at: Google Scholar
H Hemmi, T Kaisho, O Takeuchi et al., “Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway,” Nature Immunology, vol. 3, no. 2, pp. 196–200, 2002.
View at: Google Scholar
S J Gibson, J M Lindh, T R Riter et al., “Plasmacytoid dendritic cells produce cytokines and mature in response to the TLR7 agonists, imiquimod and resiquimod,” Cellular Immunology, vol. 218, no. 1-2, pp. 74–86, 2002.
View at: Google Scholar
A Ambach, B Bonnekoh, M Nguyen, M P Schön, and H Gollnick, “Imiquimod, a Toll-like receptor-7 agonist, induces perforin in cytotoxic T lymphocytes in vitro,” Molecular Immunology, vol. 40, no. 18, pp. 1307–1314, 2004.
View at: Google Scholar
F Heil, P Ahmad-Nejad, H Hemmi et al., “The Toll-like receptor 7 (TLR7)-specific stimulus loxoribine uncovers a strong relationship within the TLR7, 8 and 9 subfamily,” European Journal of Immunology, vol. 33, no. 11, pp. 2987–2997, 2003.
View at: Google Scholar
A C Gerbase, J T Rowley, D H Heymann, S F Berkley, and P Piot, “Global prevalence and incidence estimates of selected curable STDs,” Sexually Transmitted Infections, vol. 74, no. suppl 1, pp. S12–S16, 1998.
View at: Google Scholar
K A Workowski, M F Lampe, K G Wong, M B Watts, and W E Stamm, “Long-term eradication of Chlamydia trachomatis genital infection after antimicrobial therapy. Evidence against persistent infection,” JAMA: The Journal of the American Medical Association, vol. 270, no. 17, pp. 2071–2075, 1993.
View at: Google Scholar
I GM van Valkengoed, S A Morré, A JC van den Brule et al., “Follow-up, treatment, and reinfection rates among asymptomatic Chlamydia trachomatis cases in general practice,” British Journal of General Practice, vol. 52, no. 481, pp. 623–627, 2002.
View at: Google Scholar
L R Westrom, R Joesoef, G Reynolds, A Hagdu, and S E Thompson, “Pelvic inflammatory disease and fertility. A cohort study of 1,844 women with laparoscopically verified disease and 657 control women with normal laparoscopic results,” Sexually Transmitted Diseases, vol. 19, no. 4, pp. 185–192, 1992.
View at: Google Scholar
M E Ward, “The immunobiology and immunopathology of chlamydial infections,” APMIS: Acta Pathologica, Microbiologica et Immunologica Scandinavica, vol. 103, no. 11, pp. 769–796, 1995.
View at: Google Scholar
S D Hillis, L M Owens, P A Marchbanks, L F Amsterdam, and W R Mac Kenzie, “Recurrent chlamydial infections increase the risks of hospitalization for ectopic pregnancy and pelvic inflammatory disease,” American Journal of Obstetrics and Gynecology, vol. 176, no. 1 pt 1, pp. 103–107, 1997.
View at: Google Scholar
A Kinnunen, P Molander, R P Morrison et al., “Chlamydial heat shock protein 60—specific T cells in inflamed salpingeal tissue,” Fertility and Sterility, vol. 77, no. 1, pp. 162–166, 2002.
View at: Google Scholar
K A Kelly, “Cellular immunity and Chlamydia genital infection: induction, recruitment, and effector mechanisms,” International Reviews Of Immunology, vol. 22, no. 1, pp. 3–41, 2003.
View at: Google Scholar
M. Tuffrey and D. Taylor-Robinson, “Progesterone as a key factor in the development of a mouse model for genital-tract infection with Chlamydia trachomatis,” FEMS Microbiology Letters, vol. 12, no. 2, pp. 111–115, 1981.
View at: Google Scholar
J I Jr Ito, J M Lyons, and L P Airo-Brown, “Variation in virulence among oculogenital serovars of Chlamydia trachomatis in experimental genital tract infection,” Infection and Immunity, vol. 58, no. 6, pp. 2021–2023, 1990.
View at: Google Scholar
K T Ripa and P A Mårdh, “Cultivation of Chlamydia trachomatis in cycloheximide-treated mcCoy cells,” Journal of Clinical Microbiology, vol. 6, no. 4, pp. 328–331, 1977.
View at: Google Scholar
K H Ramsey, N Shaba, K P Cohoon, and K A Ault, “Imiquimod does not affect shedding of viable chlamydiae in a murine model of Chlamydia trachomatis genital tract infection,” Infectious Diseases in Obstetrics & Gynecology, vol. 11, no. 2, pp. 81–87, 2003.
View at: Google Scholar
J M Lyons, J I Jr Ito, and S A Morré, “The influence of vaginally applied imiquimod on the course of Chlamydia trachomatis serovar D infection in a murine model,” Infectious Diseases in Obstetrics & Gynecology, vol. 13, no. 1, pp. 1–3, 2005.
View at: Google Scholar
S A Morré, J M Ossewaarde, J Lan et al., “Serotyping and genotyping of genital Chlamydia trachomatis isolates reveal variants of serovars Ba, G, and J as confirmed by omp1 nucleotide sequence analysis,” Journal of Clinical Microbiology, vol. 36, no. 2, pp. 345–351, 1998.
View at: Google Scholar
J M Lyons, J I Jr Ito, A S Peña, and S A Morré, “Differences in growth characteristics and elementary body associated cytotoxicity between Chlamydia trachomatis oculogenital serovars D and H and Chlamydia muridarum,” Journal of Clinical Pathology, vol. 58, no. 4, pp. 397–401, 2005.
View at: Google Scholar
H D Caldwell, H Wood, D Crane et al., “Polymorphisms in Chlamydia trachomatis tryptophan synthase genes differentiate between genital and ocular isolates,” The Journal of Clinical Investigation, vol. 111, no. 11, pp. 1757–1769, 2003.
View at: Google Scholar
R P Morrison, “Differential sensitivities of Chlamydia trachomatis strains to inhibitory effects of gamma interferon,” Infection and Immunity, vol. 68, no. 10, pp. 6038–6040, 2000.
View at: Google Scholar
L L Perry, H Su, K Feilzer et al., “Differential sensitivity of distinct Chlamydia trachomatis isolates to IFN- $\gamma$ -mediated inhibition,” The Journal of Immunology, vol. 162, no. 6, pp. 3541–3548, 1999.
View at: Google Scholar
J I Jr Ito and J M Lyons, “Role of gamma interferon in controlling murine chlamydial genital tract infection,” Infection and Immunity, vol. 67, no. 10, pp. 5518–5521, 1999.
View at: Google Scholar
J M Carlin, Y Ozaki, G I Byrne, R R Brown, and E C Borden, “Interferons and indoleamine 2,3-dioxygenase: role in antimicrobial and antitumor effects,” Experientia, vol. 45, no. 6, pp. 535–541, 1989.
View at: Google Scholar
W L Beatty, T A Belanger, A A Desai, R P Morrison, and G I Byrne, “Tryptophan depletion as a mechanism of gamma interferon-mediated chlamydial persistence,” Infection and Immunity, vol. 62, no. 9, pp. 3705–3711, 1994.
View at: Google Scholar
D N Sauder, “Immunomodulatory and pharmacologic properties of imiquimod,” Journal of the American Academy of Dermatology, vol. 43, no. 1 pt 2, pp. S6–S11, 2000.
View at: Google Scholar
S Nair, C McLaughlin, A Weizer et al., “Injection of immature dendritic cells into adjuvant-treated skin obviates the need for ex vivo maturation,” The Journal of Immunology, vol. 171, no. 11, pp. 6275–6282, 2003.
View at: Google Scholar
M P Schön and M Schön, “Immune modulation and apoptosis induction: two sides of the antitumoral activity of imiquimod,” Apoptosis, vol. 9, no. 3, pp. 291–298, 2004.
View at: Google Scholar
R P Morrison and H D Caldwell, “Immunity to murine chlamydial genital infection,” Infection and Immunity, vol. 70, no. 6, pp. 2741–2751, 2002.
View at: Google Scholar
S A Morré, J M Lyons, and J I Jr Ito, “Murine models of Chlamydia trachomatis genital tract infection: use of mouse pneumonitis strain versus human strains,” Infection and Immunity, vol. 68, no. 12, pp. 7209–7211, 2000.
View at: Google Scholar

Copyright

Copyright © 2006 Joseph M. Lyons et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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