A novel guinea pig model of Chlamydia trachomatis genital tract infection

Jonge, Marien I. de; Keizer, Sander A.S.; Moussaoui, Hicham M. el; Dorsten, Lieke van; Azzawi, Rima; Zuilekom, Hanneke I. van; Peters, Patricia P.W.; Opzeeland, Fred J. H. van; Dijk, Laura van; Nieuwland, Rob; Roosenboom-Theunissen, Henriëtte W.M.; Vrijenhoek, Mieke P.; Debyser, Isolde; Verweij, Paul E.; Duijnhoven, Wilbert G.F. van; Bosch, J. F. van den; Nuijten, Piet J. M.

doi:10.1016/j.vaccine.2011.06.037

Cited by 11 publications

(14 citation statements)

References 25 publications

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“…C. trachomatis (CT‐D) immunization exhibited rapid bacterial clearance and significant reduction in upper genital pathology following a secondary intravaginal chlamydial challenge. These results are consistent with those from the mouse model 41 , 43 and guinea pig vaccination studies 25 , 31 wherein, robust protection against genital chlamydial challenge is induced by live chlamydial EB immunization. Hydrosalpinx (fluid‐filled oviduct dilatations) are a characteristic feature of pathological sequelae following chlamydial infections in their respective hosts.…”

Section: Discussionsupporting

confidence: 90%

“…with 1 × 10 5 IFUs of live CT‐D once and rested for 8 weeks before challenge. To achieve a sustained CT‐D infection in guinea pigs, all animals received a subcutaneous injection of 5 mg β‐estradiol (Sigma, St Louis, MO, USA) in 100 μl sesame oil (Sigma) on days −10 and −3 before challenge as described by de Jonge et al 31 All guinea pigs were anesthetized with 3% isoflurane before immunization and challenge procedures. Following challenge, vaginal swabs were collected at a 3‐day interval for 36 days from all groups of guinea pigs and plated onto HeLa cell monolayers to determine the chlamydial burden as described previously 28 …”

Section: Methodsmentioning

confidence: 99%

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Chlamydial protease‐like activity factor mediated protection against C. trachomatis in guinea pigs

Wali

Gupta

et al. 2017

Immunol Cell Biol

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We have comprehensively demonstrated using the mouse model that intranasal immunization with recombinant chlamydial protease-like activity factor (rCPAF) leads to a significant reduction in bacterial burden, genital tract pathology and preserves fertility following intravaginal genital chlamydial challenge. In the present report, we evaluated the protective efficacy of rCPAF immunization in guinea pigs, a second animal model for genital chlamydial infection. Using a vaccination strategy similar to the mouse model, we intranasally immunized female guinea pigs with rCPAF plus CpG deoxynucleotides (CpG; as an adjuvant), and challenged intravaginally with C. trachomatis serovar D (CT-D). Immunization with rCPAF/CpG significantly reduced vaginal CT-D shedding and induced resolution of infection by day 24, compared to day 33 in CpG alone treated and challenged animals. Immunization induced robust anti-rCPAF serum IgG 2 weeks following the last immunization, and was sustained at a high level 4 weeks post challenge. Upregulation of antigen specific IFN-γ gene expression was observed in rCPAF/CpG vaccinated splenocytes. Importantly, a significant reduction in inflammation in the genital tissue in rCPAF/CpG-immunized guinea pigs compared to CpG-immunized animals was observed. Taken together, this study provides evidence of the protective efficacy of rCPAF as a vaccine candidate in a second animal model of genital chlamydial infection.

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Section: Discussionsupporting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Chlamydial protease‐like activity factor mediated protection against C. trachomatis in guinea pigs

Wali

Gupta

et al. 2017

Immunol Cell Biol

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“…However, given that Ct D and Ct E are strains infecting humans, the translational value of the guinea pig model has further increased by the report of de Jonge et al on establishment of Ct D and Ct E infection in guinea pigs (de Jonge et al 2011). Using a similar model system, we observed guinea pigs (n = 5) exhibited increased levels of Ct D shedding initially from days 4–8 (85,006 ± 46,401 IFU–58,162 ± 15,106 IFU), progressively decreasing (up to day 28: 3693 ± 2485 IFU) with complete clearance of infection (no detectable bacterial shedding) after day 28 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…For sustained Ct D infection in guinea pigs, all animals received a subcutaneous injection of 5 mg β-estradiol (Sigma) in 100 µl sesame oil (Sigma) on days −10 and −3 prior to infection as described by de Jonge et al (de Jonge et al 2011). All guinea pigs were anesthetized with 3 % isoflurane before immunization and challenge procedures.…”

Section: Methodsmentioning

confidence: 99%

Guinea pig genital tract lipidome reveals in vivo and in vitro regulation of phosphatidylcholine 16:0/18:1 and contribution to Chlamydia trachomatis serovar D infectivity

Wali

Gupta

et al. 2016

Metabolomics

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Introduction Chlamydia trachomatis (Ct), is the leading cause of sexually transmitted infections worldwide. Host transcriptomic- or proteomic profiling studies have identified key molecules involved in establishment of Ct infection or the generation of anti Ct-immunity. However, the contribution of the host metabolome is not known. Objectives The objective of this study was to determine the contribution of host metabolites in genital Ct infection. Methods We used high-performance liquid chromatography-mass spectrometry, and mapped lipid profiles in genital swabs obtained from female guinea pigs at days 3, 9, 15, 30 and 65 post Ct serovar D intravaginal infection. Results Across all time points assessed, 13 distinct lipid species including choline, ethanolamine and glycerol were detected. Amongst these metabolites, phosphatidylcholine (PC) was the predominant phospholipid detected from animals actively shedding bacteria i.e., at 3, 9, and 15 days post infection. However, at days 30 and 65 when the animals had cleared the infection, PC was observed to be decreased compared to previous time points. Mass spectrometry analyses of PC produced in guinea pigs (in vivo) and 104C1 guinea pig cell line (in vitro) revealed distinct PC species following Ct D infection. Amongst these, PC 16:0/18:1 was significantly upregulated following Ct D infection (p < 0.05, >twofold change) in vivo and in vitro infection models investigated in this report. Exogenous addition of PC 16:0/18:1 resulted in significant increase in Ct D in Hela 229 cells. Conclusion This study demonstrates a role for host metabolite, PC 16:0/18:1 in regulating genital Ct infection in vivo and in vitro.

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“…caviae from the infected conjunctivae of young laboratory guinea pigs and defined it as the causative agent of guinea pig inclusion conjunctivitis [11]. The infection of guinea pigs with human Ct serovars D and E [12], and the usage of this model for Ct vaccination studies [13], was described in the genital, but not in the ocular, animal model. The major disadvantage of the ocular guinea pig model has been the lack of a wide range of immunological reagents/consumables, knockout animals, and easily accessible inbred guinea pig strains.…”

Section: Introductionmentioning

confidence: 99%

The effect of infectious dose on humoral and cellular immune responses in Chlamydophila caviae primary ocular infection

et al. 2017

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Following infection, the balance between protective immunity and immunopathology often depends on the initial infectious load. Several studies have investigated the effect of infectious dose; however, the mechanism by which infectious dose affects disease outcomes and the development of a protective immune response is not known. The aim of this study was to investigate how the infectious dose modulates the local and systemic humoral and the cellular immune responses during primary ocular chlamydial infection in the guinea pig animal model. Guinea pigs were infected by ocular instillation of a Chlamydophila caviae-containing eye solution in the conjunctival sac in three different doses: 1×102, 1×104, and 1×106 inclusion forming units (IFUs). Ocular pathology, chlamydial clearance, local and systemic C. caviae-specific humoral and cellular immune responses were assessed. All inocula of C. caviae significantly enhanced the local production of C. caviae-specific IgA in tears, but only guinea pigs infected with the higher doses showed significant changes in C. caviae-specific IgA levels in vaginal washes and serum. On complete resolution of infection, the low dose of C. caviae did not alter the ratio of CD4+ and CD8+ cells within guinea pigs’ submandibular lymph node (SMLN) lymphocytes while the higher doses increased the percentages of CD4+ and CD8+ cells within the SMLN lymphocytes. A significant negative correlation between pathology intensity and the percentage of CD4+ and CD8+ cells within SMLN lymphocyte pool at selected time points post-infection was recorded for both 1×104, and 1×106 IFU infected guinea pigs. The relevance of the observed dose-dependent differences on the immune response should be further investigated in repeated ocular chlamydial infections.

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A novel guinea pig model of Chlamydia trachomatis genital tract infection

Cited by 11 publications

References 25 publications

Chlamydial protease‐like activity factor mediated protection against C. trachomatis in guinea pigs

Chlamydial protease‐like activity factor mediated protection against C. trachomatis in guinea pigs

Guinea pig genital tract lipidome reveals in vivo and in vitro regulation of phosphatidylcholine 16:0/18:1 and contribution to Chlamydia trachomatis serovar D infectivity

The effect of infectious dose on humoral and cellular immune responses in Chlamydophila caviae primary ocular infection

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