The Roles Of Chlamydial Plasmid In Gastrointestinal Tract Colonization And In Genital Tract Infection

Chlamydia trachomatis Uro-genital tract infection is the most common sexually transmitted disease at domestic and abroad in recent years,leading to chlamydial persistent infection and a series of serious complications and sequelae.Chlamydia muridarum mice infection model is well-established model for study the mechanisms of Chlamydia trachomatis infection in human,which causes upper genital tract hydrosalpinx that highly mimics diseases development in human patients.Recent research found chlamydia in gastrointestinal tract,with the plasmid,the chlamydia may play important role in longer persistent infection and serious reproductive tract infections.Chlamydia in the mechanism of colonization in intestinal tracts,however,are still unclear,the role of chlamydial plasmid in chlamydial colonization gastrointestinal tract also not clear,and the several plasmid encoding gene function in the gastrointestinal tract colonization are also keep unknown.So it is very important to clarify the correlation and interaction between chlamydia gastrointestinal tract and genital tract.Objectives To explore the roles of chlamydial plasmid and plasmid-encoded genes in chlamydial colonization of the gastrointestinal tract and its effection on genital tract pathogenicity.Methods After 4 following on intravaginal ? intravenous?intragastric?intrarectal inoculation in C57BL/6J(n=70)and CBA/J(n=35)mice models,we detected the live chlamydia IFUs shedding with immunofluorescence assay by the vaginal and rectal swabs to observe its colonization in the gastrointestinal tract and genital tract.After infected 56,we sacrificed the mice,and observed the pathological changes both genital tract of macroscopic and microscopic histopathology.Statistics analyses the number of live organisms(IFUs)and genome copies using the Wilcoxon rank sum test.The incidence rates and hydrosalpinx score were analyzed using Fisher's exact test.After following on intravaginal ?intragastric inoculation in CBA/J(n=35)and C57BL/6J(n=35)mice models,we detected the live chlamydia IFUs shedding with immunofluorescence assay by the vaginal and rectal swabs to observe its colonization in the gastrointestinal tract and genital tract.Comparing various plasmid encoding genes in chlamydia infection the pathogenic role of genital tract and gastrointestinal tract and the correlation of genital tract disease.With C57BL/6J(n=10)and MyD88 gene knockout mice(n=10)following on transcervix and intrabursal innoculation,we detected the live chlamydia IFUs shedding with immunofluorescence assay by the genital tract tissues to observe its colonization in the genital tract.we want to further prove the evidence of native barrier to chlamydial infection in the cervix and uterus fallopian tube.The Pgp3 is a virulence factor as the role of pathogenicity.With My D88(n=15),CRAMP(n=8)knockout mice following on intravaginal and intragastric innoculation,we detected the live chlamydia IFUs shedding with immunofluorescence assay by the vaginal and rectal swabs to observe its colonization in the gastrointestinal tract and genital tract.Results 1.With the plasmid competent,the chlamydia muridarum can be transmitted from the genital tract to the gastrointestinal tract,and be able to grow robustly in the gastrointestinal tract,it had caused serious hydrosalpinx in genital infection;With the plasmid deficient,the chlamydia muridarumt spread from the genital tract chlamydia to gastrointestinal significantly delayed and reduced,and cannot colonized in the gastrointestinal tract,and also cann't cause genital tract hydrosalpinx.Even through direct intragastric inoculation,the chlamydia muridarum with plasmid deficient was very difficult or can not colonize the gastrointestinal tract.These findings showed that chlamydial plasmid played an important role in adaptation and survival in the gastrointestinal tract.It was also very important in chlamydia ascending in genital tract infection after intravaginal inoculation.2.Pgp3 and pgp4 plays a major role on chlamydial plasmid-encoded genes.The chlamydia muridarum,with pgp3 or pgp4 plasmid deficient,couldn't colonize in the gastrointestinal tract.At the same time inoculated the chlamydia muridarum,with pgp3 deficient at intrabursa I and gastrointestinal tract,pgp3 increased chlamydia muridarum pathogenic damage such as tubal scarring.It means that chlamydia cause genital tract pathogenic fibrosis,not only need the chlamydial infection and enough damages in fallopian tube/ovarian,may also depend on a second signal,named of intestinal pathogenic,which were provided by gastrointestinal tract to genital tract.Pgp3 deficient chlamydia couldn't colonize in the gastrointestinal tract,maybe it is in the persistent infection situation.Plasmid encoding gene pgp5,pgp7,pgp8 did not show pgp3 and pgp4 role.Lack of plasmid encoding gene pgp5,pgp7,pgp8,chlamydia muridarum can still inoculate and survival in gastrointestinal tract as those competent plasmids,and also show no significant differences in the gastrointestinal tract on infection ability strong or weak.3.The pgp3 deficient chlamydia muridarum could get stronger inoculate in the gastrointestinal tract and stronger infection in cervical in the My D88 knockout mice.The My D88 can keep the normal uterine tubal junction barrier function,which confirms the innate immunity played role in chlamydia defense.This function in the integration of a uterus oviduct had reduced chlamydial ascending in the genital tract infection.Conclusion The chlamydial plasmid played an important role in chlamydia muridarum inoculation in the gastrointestinal tract,even more important than in the genital tract.It was not only promote the pathogenises of chlamydia muridarum in the genital tract,but also caused chronic fibrosis through pathological immune force produced by inocuating in gastrointestinal tract.The plasmid encoding protein,pgp3,is the most important virulence factor,not only in the chlamydia inoculate in the gastrointestinal tract and genital tract infection,but also can damage the natural barrier as role of My D88 and ascending in the genital tract infection.These also reflect the important role of the intestinal microenvironment for host.