Effect of Time of Day of Infection on Chlamydia Infectivity and Pathogenesis

Stephanie R Lundy,Tankya Simoneaux,Debra Ellerson,Ward Kirlin,Jason P Debruyne,Zenas George,Yusuf O Omosun,Joseph U Igietseme,Ifeyinwa Benyeogor,Carolyn M Black,Tarek Ahmad,Qing He,Uriel Blas-Machado,Francis O Eko,Tolulope Omosun,Yemaya Robinson

doi:10.1038/s41598-019-47878-y

Stephanie R Lundy, Tankya Simoneaux + Show 14 more

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https://doi.org/10.1038/s41598-019-47878-y

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Genital chlamydia infection in women causes complications such as pelvic inflammatory disease and tubal factor infertility, but it is unclear why some women are more susceptible than others. Possible factors, such as time of day of chlamydia infection on chlamydial pathogenesis has not been determined. We hypothesised that infections during the day, will cause increased complications compared to infections at night. Mice placed under normal 12:12 light: dark (LD) cycle were infected intravaginally with Chlamydia muridarum either at zeitgeber time 3, ZT3 and ZT15. Infectivity was monitored by periodic vaginal swabs and chlamydiae isolation. Blood and vaginal washes were collected for host immunologic response assessments. The reproductive tracts of the mice were examined histopathologically, and fertility was determined by embryo enumeration after mating. Mice infected at ZT3 shed significantly more C. muridarum than mice infected at ZT15. This correlated with the increased genital tract pathology observed in mice infected at ZT3. Mice infected at ZT3 were less fertile than mice infected at ZT15. The results suggest that the time of day of infection influences chlamydial pathogenesis, it indicates a possible association between complications from chlamydia infection and host circadian clock, which may lead to a better understanding of chlamydial pathogenesis.

Highlights

Genital chlamydia infection, a sexually transmitted infection (STI), which is caused by the bacteria C. trachomatis, is the most commonly reported bacterial STI in the United States
We hypothesized that genital chlamydia infection is regulated by circadian clocks present in the infected organisms, this study was not designed to discern between circadian rhythms directed by the suprachiasmatic nucleus (SCN) or the oscillations of immune modulators directed by the circadian clocks in the immune cells
Our results revealed that under normal light: dark (LD) conditions, mice infected at the early active period shed less bacteria and cleared the infection faster compared to mice infected during the early rest period

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Introduction

A sexually transmitted infection (STI), which is caused by the bacteria C. trachomatis, is the most commonly reported bacterial STI in the United States. Albumin D-box binding protein (DBP) and the repressor nuclear factor interleukin 3 (NFIL3 or E4BP4) form an extra loop, which regulates transcription of genes containing D-box, sequences, including Period These rhythmic feedback mechanisms generate oscillations in gene expression that convey circadian timing cues to cellular processes[12]. The innate and adaptive immune system in mice and human have been shown to be regulated by endogenous circadian clocks[29] They have been reported to display daily rhythms of cell counts in blood and peripheral lymphoid organs, lymphocyte proliferation, and in vitro stimulated cytokine levels[29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44]. The current study was designed to determine the influence of time of day on chlamydia infection and complications, to help us better understand the processes involved in chlamydia pathogenesis that leads to infertility

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