Does Active Oral Sex Contribute to Female Infertility?

Bavoil, Patrik M.; Marques, Patrícia X.; Brotman, Rebecca M.

doi:10.1093/infdis/jix419

Cited by 41 publications

(43 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…C. muridarum readily spreads from the genital tract to the GI tract and persists in the colon for long periods of time (6,17,21,22,44). Although GI Chlamydia is nonpathogenic to the GI tract (21,24), it may impact chlamydial pathogenicity in the genital tract by either serving as a reservoir for repeatedly infecting the genital tract (6,7,20) or inducing profibrotic responses to exacerbate pathology in the upper genital tract (23). On the other hand, the chlamydial colonization in the GI FIG 5 IFN-␥ deficiency is sufficient for rescuing orally delivered chromosomal mutant G28.51.1 to colonize the gastrointestinal tract.…”

Section: Discussionmentioning

confidence: 99%

Distinct Roles of Chromosome- versus Plasmid-Encoded Genital Tract Virulence Factors in Promoting Chlamydia muridarum Colonization in the Gastrointestinal Tract

et al. 2019

View full text Add to dashboard Cite

The genital pathogen Chlamydia is known to colonize the gastrointestinal tract. Orally delivered Chlamydia muridarum can reach the colon and maintain a long-lasting colonization there. However, C. muridarum with mutations in chromosomal genes tc0237 and tc0668 (designated a chromosomal mutant) or deficient in plasmid-encoded pGP3 (designated a plasmid mutant) is unable to do so. We now report that the chromosomal mutant is still able to reach the colon while the plasmid mutant fails to do so following an oral delivery, suggesting that lack of colon colonization by different mutants may involve distinct mechanisms. Consistently, a direct intracolonic delivery selectively restored the ability of the plasmid mutant, but not the chromosomal mutant, to colonize the colon. The chromosomal mutant was rescued only in the colon of mice deficient in gamma interferon (IFN-␥). Thus, the chromosomal mutant's deficiency in colonizing colonic mucosal tissue is likely due to its increased susceptibility to IFN-␥-mediated immunity. Furthermore, IFN-␥ deficiency was sufficient for rescuing colon colonization of an orally delivered chromosomal mutant but not plasmid mutant while mice deficient in gastric acid production rescued the plasmid mutant but not the chromosomal mutant. Both mutants are attenuated in inducing genital tract pathology. Thus, we propose that chlamydial chromosomal-gene-encoded genital tract virulence factors may be essential for Chlamydia to maintain long-lasting colonization in the colon while the plasmid may enable Chlamydia to reach the colon by promoting evasion of gastric barriers.

show abstract

Section: Discussionmentioning

confidence: 99%

Distinct Roles of Chromosome- versus Plasmid-Encoded Genital Tract Virulence Factors in Promoting Chlamydia muridarum Colonization in the Gastrointestinal Tract

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Chlamydia has been frequently detected in the GI tracts of both humans (14-17) and animals (20,(23)(24)(25). C. trachomatis in the GI tract has been proposed to serve as a reservoir for promoting chlamydial pathogenicity in women's genital tracts (18,19), while C. muridarum has been shown to readily spread to the GI tract (20), which may indirectly promote chlamydial pathogenicity in mouse genital tracts (22). However, when a naive mouse is first exposed to C. muridarum in the GI tract, the GI tract C. muridarum may act as an oral vaccine to induce transmucosal immunity (32,33).…”

Section: Discussionmentioning

confidence: 99%

Antigen-Specific CD4⁺T Cell-Derived Gamma Interferon Is Both Necessary and Sufficient for ClearingChlamydiafrom the Small Intestine but Not the Large Intestine

Lin

Koprivsek

et al. 2019

Infect Immun

View full text Add to dashboard Cite

The genital tract pathogen Chlamydia trachomatis is frequently detected in the gastrointestinal tract, but the host immunity that regulates chlamydial colonization in the gut remains unclear. In a Chlamydia muridarum-C57 mouse model, chlamydial organisms are cleared from the genital tract in ϳ4 weeks, but the genital organisms can spread to the gastrointestinal tract. We found that the gastrointestinal chlamydial organisms were cleared from the small intestine by day 28, paralleling their infection course in the genital tract, but persisted in the large intestine for long periods. Mice deficient in ␣/␤ T cells or CD4 ϩ T cells but not CD8 ϩ T cells showed chlamydial persistence in the small intestine, indicating a critical role for CD4 ϩ T cells in clearing Chlamydia from the small intestine. The CD4 ϩ T cell-dependent clearance is likely mediated by gamma interferon (IFN-␥), since mice deficient in IFN-␥ but not interleukin 22 (IL-22) signaling pathways rescued chlamydial colonization in the small intestine. Furthermore, exogenous IFN-␥ was sufficient for clearing Chlamydia from the small intestine but not the large intestine. Mice deficient in developing Chlamydia-specific Th1 immunity showed chlamydial persistence in the small intestine. Finally, IFN-␥-producing CD4 ϩ but not CD8 ϩ T cells from immunized donor mice were sufficient for eliminating Chlamydia from the small intestine but not the large intestine of recipient mice. Thus, we have demonstrated a critical role for Th1 immunity in clearing Chlamydia from the small intestine but not the large intestine, indicating that chlamydial colonization in different regions of the gastrointestinal tract is regulated by distinct immune mechanisms.

show abstract

“…In addition to the urogenital tract, C. trachomatis infects the conjunctiva, pharynx, respiratory tract, rectum, and gastrointestinal (GI) tract. The recent recognition that rectal infections are frequent in women who do not report traditional rectal chlamydia infection risk factors ( 6 ), and the premise that the GI tract may serve as a site for persisting infection and as a reservoir for urogenital reinfection ( 7 – 10 ), has renewed interest in understanding the molecular basis of chlamydial GI colonization and pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Chlamydia muridarum Genital and Gastrointestinal Infection Tropism Is Mediated by Distinct Chromosomal Factors

et al. 2018

View full text Add to dashboard Cite

Some members of the genus Chlamydia, including the human pathogen Chlamydia trachomatis, infect multiple tissues, including the genital and gastrointestinal (GI) tracts. However, it is unknown if bacterial targeting to these sites is mediated by multifunctional or distinct chlamydial factors. We previously showed that disruption of individual large clostridial toxin homologs encoded within the Chlamydia muridarum plasticity zone were not critical for murine genital tract infection. Here, we assessed whether cytotoxin genes contribute to C. muridarum GI tropism. Infectivity and shedding of wild-type (WT) C. muridarum and three mutants containing nonsense mutations in different cytotoxin genes, tc0437, tc0438, and tc0439, were compared in mouse genital and GI infection models. One mutant, which had a nonsense mutation in tc0439, was highly attenuated for GI infection and had a GI 50% infectious dose (ID50) that was 1,000 times greater than that of the WT. GI inoculation with this mutant failed to elicit anti-chlamydial antibodies or to protect against subsequent genital tract infection. Genome sequencing of the tc0439 mutant revealed additional chromosomal mutations, and phenotyping of additional mutants suggested that the GI attenuation might be linked to a nonsense mutation in tc0600. The molecular mechanism underlying this dramatic difference in tissue-tropic virulence is not fully understood. However, isolation of these mutants demonstrates that distinct chlamydial chromosomal factors mediate chlamydial tissue tropism and provides a basis for vaccine initiatives to isolate chlamydia strains that are attenuated for genital infection but retain the ability to colonize the GI tract and elicit protective immune responses.

show abstract

Does Active Oral Sex Contribute to Female Infertility?

Cited by 41 publications

References 25 publications

Distinct Roles of Chromosome- versus Plasmid-Encoded Genital Tract Virulence Factors in Promoting Chlamydia muridarum Colonization in the Gastrointestinal Tract

Distinct Roles of Chromosome- versus Plasmid-Encoded Genital Tract Virulence Factors in Promoting Chlamydia muridarum Colonization in the Gastrointestinal Tract

Antigen-Specific CD4⁺T Cell-Derived Gamma Interferon Is Both Necessary and Sufficient for ClearingChlamydiafrom the Small Intestine but Not the Large Intestine

Chlamydia muridarum Genital and Gastrointestinal Infection Tropism Is Mediated by Distinct Chromosomal Factors

Contact Info

Product

Resources

About

Does Active Oral Sex Contribute to Female Infertility?

Cited by 41 publications

References 25 publications

Distinct Roles of Chromosome- versus Plasmid-Encoded Genital Tract Virulence Factors in Promoting Chlamydia muridarum Colonization in the Gastrointestinal Tract

Distinct Roles of Chromosome- versus Plasmid-Encoded Genital Tract Virulence Factors in Promoting Chlamydia muridarum Colonization in the Gastrointestinal Tract

Antigen-Specific CD4+T Cell-Derived Gamma Interferon Is Both Necessary and Sufficient for ClearingChlamydiafrom the Small Intestine but Not the Large Intestine

Chlamydia muridarum Genital and Gastrointestinal Infection Tropism Is Mediated by Distinct Chromosomal Factors

Contact Info

Product

Resources

About

Antigen-Specific CD4⁺T Cell-Derived Gamma Interferon Is Both Necessary and Sufficient for ClearingChlamydiafrom the Small Intestine but Not the Large Intestine