Complement Factor C5 but Not C3 Contributes Significantly to Hydrosalpinx Development in Mice Infected with Chlamydia muridarum

Yang, Zhangsheng; Conrad, Turner; Zhou, Zhou; Chen, Jianlin; Dutow, Pavel; Klos, Andreas; Zhong, Guangming

doi:10.1128/iai.01833-14

Cited by 36 publications

(39 citation statements)

References 58 publications

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“…The hydrosalpinx incidence and severity scores for the mice listed in Table 2 are summarized in Table 3. As reported previously, mice deficient in complement factor C5 failed to develop hydrosalpinx (26), and deficiency in IL-1R1 also significantly reduced the development of hydrosalpinx (43). However, mice deficient in MyD88 developed more severe hydrosalpinx (12).…”

Section: Fig 6 Effect Of Plasmid Depletion and Infection Routes On Cmentioning

confidence: 47%

“…Since Ͼ50% of the mice were induced to develop uterine horn dilation by C. muridarum infection and none of the uninfected mice developed any significant uterine dilation, we concluded that the uterine horn dilation was induced by C. muridarum infection. The hydrosalpinx from the same set of mice was also noted, and some of the results were previously published (8,15,26,28,41). Although mice with more severe uterine horn dilation seemed to lack hydrosalpinx in the oviduct in some cases, there was no significant correlation between uterine horn dilation and oviduct hydrosalpinx when all 88 mice were taken into consideration.…”

Section: Muridarum Induces Uterine Horn Dilation In Mice Followingmentioning

confidence: 51%

“…The following strains of wild-type and knockout (KO) mice used in the current study were all purchased from Jackson Laboratories (Bar Harbor, ME): C57BL/6J (JAX [Jackson Laboratories] stock number 000664), BALB/cJ (000651), C3H/HeJ (000659), TRIF KOs (005037), TIRAP KOs (017629), JNK2 KOs (004321), interleukin 1 receptor type I (IL-1R1) KOs (003245), IL-10 KOs (002251), and gamma interferon (IFN-␥) KOs (002287; 2 died before sacrifice). The pathology data for the remaining strains of mice used in the current study were acquired from the images and/or tissues of mice sacrificed in previous studies (8,15,24,26,28,41). The infection procedures were as follows.…”

Section: Methodsmentioning

confidence: 99%

“…Thus, it is necessary to characterize the C. muridarum-induced uterine horn dilation. Many previous mouse model-based studies grouped both hydrosalpinx and uterine horn dilation as upper genital tract pathology (19,20) and focused only on the fertility outcome (21)(22)(23) or patency of the upper genital tract (6) without differentiating uterine horn dilation from hydrosalpinx (8,(24)(25)(26)(27)(28). Although a previous study reported that interferon regulatory transcription factor 3 (IRF3) protected mice from uterine horn pathology during C. muridarum infection (13) and efforts have also been made to define host factors involved in C. muridarum induction of uterine horn dilation (29), the pathological basis of uterine horn dilation remains unclear.…”

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confidence: 99%

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Chlamydia muridarum Induction of Glandular Duct Dilation in Mice

et al. 2015

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Although Chlamydia-induced hydrosalpinx in women and mice has been used as a surrogate marker for tubal infertility, the medical relevance of nontubal pathologies, such as uterine horn dilation, developed in mice following chlamydial infection remains unclear. We now report that the uterine horn dilation correlates with glandular duct dilation detected microscopically following Chlamydia muridarum infection. The dilated glandular ducts pushed the uterine horn lumen to closure or dilation and even broke through the myometrium to develop extrusion outside the uterine horn. The severity scores of uterine horn dilation observed macroscopically correlated well with the number of cross sections of the dilated glandular ducts counted under microscopy. Chlamydial infection was detected in the glandular epithelial cells, potentially leading to inflammation and dilation of the glandular ducts. Direct delivery of C. muridarum into the mouse uterus increased both uterine horn/glandular duct dilation and hydrosalpinx. However, the chlamydial plasmid, which is essential for the induction of hydrosalpinx, was not required for the induction of uterine horn/glandular duct dilation. Screening 12 strains of mice for uterine horn dilation following C. muridarum infection revealed that B10.D2, C57BL/10J, and C57BL/6J mice were most susceptible, followed by BALB/cJ and A/J mice. Deficiency in host genes involved in immune responses failed to significantly alter the C. muridarum induction of uterine horn dilation. Nevertheless, the chlamydial induction of uterine horn/glandular duct dilation may be used to evaluate plasmidindependent pathogenicity of Chlamydia in susceptible mice.

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Section: Fig 6 Effect Of Plasmid Depletion and Infection Routes On Cmentioning

confidence: 47%

Section: Muridarum Induces Uterine Horn Dilation In Mice Followingmentioning

confidence: 51%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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Chlamydia muridarum Induction of Glandular Duct Dilation in Mice

et al. 2015

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“…This is because a single inoculation of C. muridarum organisms in the mouse lower genital tract can cause hydrosalpinx and infertility (7)(8)(9), closely mimicking the tubal adhesion, hydrosalpinx, and infertility observed in women urogenitally infected with C. trachomatis (10)(11)(12). Although C. muridarum is not a natural sexually transmitted agent of mice, chlamydiologists have used this model not only to identify both chlamydial (13)(14)(15)(16)(17) and host (1,5,(18)(19)(20)(21)(22)(23)(24) pathogenic determinants but also to define the roles of ascending infection and tubal inflammation in chlamydial induction of hydrosalpinx (9,16,25,26). Nevertheless, questions such as how a self-limited infection with C. muridarum in the mouse genital tract can trigger tubal fibrosis or hydrosalpinx that lasts long after the tubal infection is resolved (9,25) remain unanswered.…”

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Intravenous Inoculation with Chlamydia muridarum Leads to a Long-Lasting Infection Restricted to the Gastrointestinal Tract

et al. 2016

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cChlamydia has been detected in the gastrointestinal tracts of both animals and humans. However, it remains unclear whether the chlamydial organisms can be introduced into the gastrointestinal tract via pathways independent of the oral and anal routes. We have recently shown that Chlamydia muridarum spreads from the genital tract to the gastrointestinal tract potentially via the circulatory system. To test whether hematogenous C. muridarum can spread to and establish a long-lasting colonization in the mouse gastrointestinal tract, we inoculated mice intravenously with a luciferase-expressing C. muridarum strain and monitored its distribution. After tail vein inoculation, most luciferase-generated bioluminescence signals were detected in the mouse abdominal area throughout the experiment. The ex vivo imaging revealed that the abdominal signals came from the gastrointestinal tract tissues. Simultaneous monitoring of chlamydial organisms in individual organs or tissues revealed an initial stage of systemic spreading followed by a long-lasting infection in the gastrointestinal tract. A retro-orbital vein inoculation of the C. muridarum organisms at a lower dose in a different mouse strain also led to colonization of the gastrointestinal tract. We have demonstrated that intravenous C. muridarum inoculation can result in colonization of the gastrointestinal tract, suggesting that the chlamydial organisms may use the sexual behavior-independent circulation pathway to infect the gastrointestinal tract.C hlamydia muridarum infection in the mouse genital tract model has been used for investigation of the mechanisms of Chlamydia trachomatis pathogenesis and immune responses (1-6). This is because a single inoculation of C. muridarum organisms in the mouse lower genital tract can cause hydrosalpinx and infertility (7-9), closely mimicking the tubal adhesion, hydrosalpinx, and infertility observed in women urogenitally infected with C. trachomatis (10-12). Although C. muridarum is not a natural sexually transmitted agent of mice, chlamydiologists have used this model not only to identify both chlamydial (13-17) and host (1, 5, 18-24) pathogenic determinants but also to define the roles of ascending infection and tubal inflammation in chlamydial induction of hydrosalpinx (9,16,25,26). Nevertheless, questions such as how a self-limited infection with C. muridarum in the mouse genital tract can trigger tubal fibrosis or hydrosalpinx that lasts long after the tubal infection is resolved (9, 25) remain unanswered.Although C. trachomatis is a sexually transmitted bacterial pathogen that causes pathologies in the genital tract (27, 28), it has also been detected in the gastrointestinal (GI) tract of humans (29-32). C. muridarum colonized the mouse GI tract when it was introduced to multiple mucosae (33) and established a long-lasting infection when directly inoculated into the mouse GI tract (34,35). The question is whether persistent colonization of the mouse GI tract can fill in the temporal gap between the self-limited infection...

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