Murine host response to Neisseria gonorrhoeae upper genital tract infection reveals a common transcriptional signature, plus distinct inflammatory responses that vary between reproductive cycle phases

Francis, Ian; Islam, Epshita A.; Gower, Adam C.; Shaik‐Dasthagirisaheb, Yazdani B.; Gray-Owen, Scott D.; Wetzler, Lee M.

doi:10.1186/s12864-018-5000-7

Cited by 13 publications

(11 citation statements)

References 72 publications

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“…Animal models have been largely used to study microbiota, especially in the case of human gut microbiota [62]. Concerning bacteria colonizing the genital tract, murine vaginal and uterine models of infection have been used to study human pathogens like Chlamydia trachomatis [63,64,65], Mycoplasma genitalium [66,67,68], or Neisseria gonorrhoeae [69,70,71]. However, while useful to dissect the infectious process, murine genital models have important physiological differences compared to the human vagina, which in its healthy state is colonized mainly by Lactobacillus spp.…”

Section: Experimental Assessment Of the Role Of Uterine Microbiotamentioning

confidence: 99%

Bacterial Colonization of the Female Upper Genital Tract

Peric

Weiß

Vulliemoz

et al. 2019

IJMS

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Bacteria colonize most of the human body, and the female genital tract is not an exception. While the existence of a vaginal microbiota has been well established, the upper genital tract has been considered a sterile environment, with a general assumption that bacterial presence is associated with adverse clinical manifestation. However, recent metagenomic studies identified specific patterns of microbiota colonizing the uterus, fallopian tubes, ovaries, and placenta. These results need confirmation and further investigations since the data are only scarce. Bacterial colonization of these sites appears different from the vaginal one, despite evidence that vaginal bacteria could ascend to the upper genital tract through the cervix. Are these bacteria only commensal or do they play a role in the physiology of the female upper genital tract? Which are the genera that may have a negative and a positive impact on the female reproductive function? The aim of this review is to critically present all available data on upper genital tract microbiota and discuss its role in human reproduction, ranging from the technical aspects of these types of analyses to the description of specific bacterial genera. Although still very limited, research focusing on genital colonization of bacteria other than the vaginal milieu might bring novel insights into physiopathology of human reproduction.

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Section: Experimental Assessment Of the Role Of Uterine Microbiotamentioning

confidence: 99%

Bacterial Colonization of the Female Upper Genital Tract

Peric

Weiß

Vulliemoz

et al. 2019

IJMS

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“…In addition to the direct effect of Opa binding on epithelial attachment, this outcome is facilitated by decreased exfoliation of infected epithelial cells due to the CEACAM-dependent upregulation of β1 integrin-mediated binding to their underlying extracellular matrix (155). However, the effect of CEACAM expression depends on the exposed tissue and stage of the female reproductive cycle since, for example, uterine inflammation occurs in transcervically infected wild-type mice in diestrus (156) but occurs only in the presence of human CEACAM1 when the mice are in estrus (94, 157). Moreover, the integration of CEACAM-dependent effects determines the outcome of infection since neutrophil expression of CEACAM3 promotes inflammation and phagocytic clearance of the gonococci, effectively opposing the infection-promoting contribution of epithelial CEACAMs (88, 94).…”

Section: Animal Modelsmentioning

confidence: 99%

Progress Toward a Gonococcal Vaccine: The Way Forward

2019

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The concept of immunizing against gonorrhea has received renewed interest because of the recent emergence of strains of Neisseria gonorrhoeae that are resistant to most currently available antibiotics, an occurrence that threatens to render gonorrhea untreatable. However, despite efforts over many decades, no vaccine has yet been successfully developed for human use, leading to pessimism over whether this goal was actually attainable. Several factors have contributed to this situation, including extensive variation of the expression and specificity of many of the gonococcal surface antigens, and the ability of N. gonorrhoeae to resist destruction by complement and other innate immune defense mechanisms. The natural host restriction of N. gonorrhoeae for humans, coupled with the absence of any definable state of immunity arising from an episode of gonorrhea, have also complicated efforts to study gonococcal pathogenesis and the host's immune responses. However, recent findings have elucidated how the gonococcus exploits and manipulates the host's immune system for its own benefit, utilizing human-specific receptors for attachment to and invasion of tissues, and subverting adaptive immune responses that might otherwise be capable of eliminating it. While no single experimental model is capable of providing all the answers, experiments utilizing human cells and tissues in vitro, various in vivo animal models, including genetically modified strains of mice, and both experimental and observational human clinical studies, have combined to yield important new insight into the immuno-pathogenesis of gonococcal infection. In turn, these have now led to novel approaches for the development of a gonococcal vaccine. Ongoing investigations utilizing all available tools are now poised to make the development of an effective human vaccine against gonorrhea an achievable goal within a foreseeable time-frame.

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“…Although transgenic animals are promising models for studying the early stages of N. gonorrhoeae infection (Wang et al, 2008;Gu et al, 2010;Francis et al, 2018), they cannot fully recapitulate all the features of gonorrhea in humans (Wang et al, 2017a;Quillin and Seifert, 2018;. Nevertheless, only a few non-transgenic animal models such as chimpanzees were successfully infected by N. gonorrhoeae and showed a greater resemblance of the symptoms and host reaction (Kraus et al, 1975).…”

Section: Animal Modelsmentioning

confidence: 99%

“…(Xu et al, 2018) hCEACAM1, CEABAC2 and hCEACAM5 transgenic mice Transcriptional analysis of infected mice; mice diestrus uterine infection shows higher type-1 interferon induction. (Francis et al, 2018) Estradiol treated female BALB/c mice Commensal species of Neisseria kill Ngo through a mechanism based on genetic competence and DNA methylation state. (Kim et al, 2019) An invertebrate Galleria mellonella greater wax moth larvae…”

Section: In Vitro 2d Cell Modelsmentioning

confidence: 99%

Tissue Models for Neisseria gonorrhoeae Research—From 2D to 3D

Heydarian

Rühl

Rawal

et al. 2022

Front. Cell. Infect. Microbiol.

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Neisseria gonorrhoeae is a human-specific pathogen that causes gonorrhea, the second most common sexually transmitted infection worldwide. Disease progression, drug discovery, and basic host-pathogen interactions are studied using different approaches, which rely on models ranging from 2D cell culture to complex 3D tissues and animals. In this review, we discuss the models used in N. gonorrhoeae research. We address both in vivo (animal) and in vitro cell culture models, discussing the pros and cons of each and outlining the recent advancements in the field of three-dimensional tissue models. From simple 2D monoculture to complex advanced 3D tissue models, we provide an overview of the relevant methodology and its application. Finally, we discuss future directions in the exciting field of 3D tissue models and how they can be applied for studying the interaction of N. gonorrhoeae with host cells under conditions closely resembling those found at the native sites of infection.

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Murine host response to Neisseria gonorrhoeae upper genital tract infection reveals a common transcriptional signature, plus distinct inflammatory responses that vary between reproductive cycle phases

Cited by 13 publications

References 72 publications

Bacterial Colonization of the Female Upper Genital Tract

Bacterial Colonization of the Female Upper Genital Tract

Progress Toward a Gonococcal Vaccine: The Way Forward

Tissue Models for Neisseria gonorrhoeae Research—From 2D to 3D

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