title: Viral infection of the pregnant cervix predisposes to ascending bacterial infection.
abstract: Preterm birth is the major cause of neonatal mortality and morbidity, and bacterial infections that ascend from the lower female reproductive tract are the most common route of uterine infection leading to preterm birth. The uterus and growing fetus are protected from ascending infection by the cervix, which controls and limits microbial access by the production of mucus, cytokines, and antimicrobial peptides. If this barrier is compromised, bacteria may enter the uterine cavity, leading to preterm birth. Using a mouse model, we demonstrate, to our knowledge for the first time, that viral infection of the cervix during pregnancy reduces the capacity of the female reproductive tract to prevent bacterial infection of the uterus. This is due to differences in susceptibility of the cervix to infection by virus during pregnancy and the associated changes in TLR and antimicrobial peptide expression and function. We suggest that preterm labor is a polymicrobial disease, which requires a multifactorial approach for its prevention and treatment.
authors.affiliation: Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Racicot
authors.forename: Ingrid
authors.initials: I
authors.lastname: Cardenas
authors.forename: Vera
authors.initials: V
authors.lastname: Wünsche
authors.forename: Paulomi
authors.initials: P
authors.lastname: Aldo
authors.forename: Seth
authors.initials: S
authors.lastname: Guller
authors.forename: Robert E
authors.initials: RE
authors.lastname: Means
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Gil
authors.initials: G
authors.lastname: Mor
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000276:immunology* / Q000382:microbiology; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D004927:Escherichia coli Infections / Q000276:immunology / Q000382:microbiology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology; D006566:Herpesviridae Infections / Q000276:immunology* / Q000821:virology; D016023:Integrins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D047928:Premature Birth / Q000209:etiology; D051193:Toll-Like Receptors / Q000378:metabolism; D016869:Ureaplasma Infections / Q000276:immunology / Q000382:microbiology; D002577:Uterine Cervical Diseases / Q000276:immunology / Q000821:virology*; D014591:Uterine Diseases / Q000276:immunology* / Q000382:microbiology / Q000821:virology
chemical_list: D012739:Gonadal Steroid Hormones; D016023:Integrins; D051193:Toll-Like Receptors