Animal model studies of genital chlamydial infections. Immunity to re-infection with guinea-pig inclusion conjunctivitis agent in the urethra and eye of male guinea-pigs.

Howard, L V; O'Leary, Maura; Nichols, Roger

doi:10.1136/sti.52.4.261

Cited by 19 publications

(17 citation statements)

References 11 publications

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“…The animals were subsequently challenged with the same serovar or the alternate serovar and were found to be protected. Similarly, Howard et al (12) and Patterson and Rank (30) initiated the characterization of the immune response to reinfection in the guinea pig model. Male animals inoculated in the urethra with the GPIC agent developed urethritis.…”

Section: Discussionmentioning

confidence: 99%

New Murine Model for the Study of Chlamydia trachomatis Genitourinary Tract Infections in Males

2004

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The lack of an experimental model has significantly limited the understanding of the pathogenesis of Chlamydia trachomatis infections in males. In an attempt to establish a model using the natural route of infection, we inoculated male mice in the meatus urethra. To establish the 50% infectious dose (ID 50 ), C3H/HeN (H-2 k ) male mice were inoculated in the meatus urethra with doses ranging from 10 1 to 10 7 inclusion-forming units (IFU) of C. trachomatis mouse pneumonitis biovar (MoPn) and were euthanized at 10 days postinfection (p.i.). Approximately 50% of the animals inoculated with 5 ؋ 10 4 IFU had positive cultures of the urethra, urinary bladder, epididymides, and/or testes. Subsequently, to characterize the course of the infection, a group of animals was inoculated with 10 6 IFU/mouse (20 times the ID 50 ). Positive cultures from the urethra, urinary bladder, epididymides, and testes were obtained from the animals. The infection peaked in the first 2 weeks p.i. and subsequently declined over the 7 weeks of observation. C. trachomatis-specific antibodies were first detected in serum by 2 weeks p.i. and rose over the period of observation. The titers of immunoglobulin G2a (IgG2a) were 16-fold higher than those of IgG1. A lymphoproliferative assay using splenocytes and local lymph nodes showed a strong cell-mediated immune response. Levels of gamma interferon were significantly higher than those of interleukin-4 in the supernatants from stimulated lymphocytes. An acute inflammatory infiltrate consisting of polymorphonuclear leukocytes was detected in the urethra at 1 week p.i. At 3 weeks p.i., a mixed acute and chronic inflammatory infiltrate was observed in the urethra that by 5 to 6 weeks was mainly composed of mononuclear cells. Similar findings were also observed in the urinary bladder, although the inflammatory infiltrate was delayed by approximately a week relative to that in the urethra. Sections of the epididymides showed a focal acute inflammatory infiltrate at 2 weeks p.i. Immunohistochemical staining demonstrated multiple chlamydial inclusions in the epithelium of the urethra and urinary bladder. No chlamydial inclusions were observed in the epididymides or testes. In conclusion, inoculation of male mice in the meatus urethra with C. trachomatis MoPn results in an infection of the genitourinary tract that closely parallels that described in humans. This model should help to characterize the pathogenesis of chlamydial infections in males and to test therapeutic and preventive measures.

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Section: Discussionmentioning

confidence: 99%

New Murine Model for the Study of Chlamydia trachomatis Genitourinary Tract Infections in Males

2004

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“…The model has, however, some relevance to the study of human chlamydial oculogenital infections because intraurethral inoculation of male animals results in an infection which may be transmitted to the genital tract of the female, and thence to the eye of the offspring.186 Male animals so infected become completely resistant to reinfection of the urethra but are still susceptible to infection of the eye four to six weeks later. 187 Vaginal infection also provides immunity of a similar kind. '88 189 Infection of the eye, however, results in resistance not only to ocular but also to genital infection six weeks later.…”

Section: Vaccination Prospectsmentioning

confidence: 99%

The rôle of Chlamydia trachomatis in genital-tract and associated diseases.

Taylor‐Robinson¹,

Thomas²

1980

J Clin Pathol

165

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“…In the case of the guinea pig model, males have been infected with the C. psittaci guinea pig inclusion conjunctivitis (GPIC) agent (also called Chlamydia caviae ) [30–32]. For example, Howard et al [32] inoculated male guinea pigs in the urethra with GPIC.…”

Section: Discussionmentioning

confidence: 99%

A new murine model for testing vaccines against genital Chlamydia trachomatis infections in males

Pal

Sarcon

Maza

2010

Vaccine

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Two groups of 50 BALB/c male mice were immunized with live Chlamydia trachomatis mouse pneumonitis (MoPn) using the intranasal (i.n.) or the meatus urethra (intraurethral: i.u.) routes. As a control group, 100 male mice were sham-immunized in parallel. Both groups of animals vaccinated with live organisms developed strong Chlamydia-specific humoral and cell mediated immune responses. Based on the IgG2a/IgG1 ratio and the levels of IFN-γ both groups mounted a Th1 immune response. At six weeks following the immunization, all mice were challenged in the meatus urethra. The urethra, urinary bladder, testes and epididymides were harvested at weekly intervals and tested for the presence of C. trachomatis. Based on the culture results from these four organs both groups of Chlamydia-immunized mice showed significant protection. In the group immunized i.u., 10% (5/50) had positive cultures, while in the group immunized i.n. 28% (14/50) had positive cultures during the 5 weeks of observation. In contrast, in the sham-immunized animals 47% (47/100) had positive cultures (P<0.005) during the study period. In addition, the number of positive organs, the length of time that the animal had positive cultures, and the total number of inclusion forming units (IFU) recovered were overall significantly lower in the i.u. or i.n. groups in comparison with the sham-immunized animals. However, in relation to the i.u. immunized group, the protection elicited in the i.n. group was delayed and not as robust. In conclusion, immunization of mice in the meatus urethra may provide the gold standard for testing Chlamydia vaccines in a male model.

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Animal model studies of genital chlamydial infections. Immunity to re-infection with guinea-pig inclusion conjunctivitis agent in the urethra and eye of male guinea-pigs.

Cited by 19 publications

References 11 publications

New Murine Model for the Study of Chlamydia trachomatis Genitourinary Tract Infections in Males

New Murine Model for the Study of Chlamydia trachomatis Genitourinary Tract Infections in Males

The rôle of Chlamydia trachomatis in genital-tract and associated diseases.

A new murine model for testing vaccines against genital Chlamydia trachomatis infections in males

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