Interaction between Pathogenic Bacteria and Intrauterine Leukocytes Triggers Alternative Molecular Signaling Cascades Leading to Labor in Women

Abstract

Increased risk of preterm labor has been linked to cervicovaginal infection with Ureaplasma urealyticum and group B streptococci. Although various experimental models have been developed to study the role of amniochorion infection in preterm labor, they typically exclude the initial interaction between intrauterine leukocytes (recruited from decidual vessels into the avascular fetal membranes) and infecting bacteria. In this work, we ascertained whether inflammatory molecules secreted by bacterium-activated intrauterine leukocytes stimulate the amniochorion production of mediators involved in human labor. Using a two-step process beginning with placental circulating leukocytes as a proxy for intrauterine leukocytes, we found that coincubation of amniochorion explants with plasma from placental whole blood preincubated with group B streptococci resulted in a significant increase in tumor necrosis factor alpha (TNF-␣) and matrix metalloproteinase 9 (MMP-9) levels in tissue. Extensive changes in the connective tissue arrangement and a decrease in collagen content demonstrated the degradation of the extracellular matrix following this treatment. In contrast, plasma from blood preconditioned with U. urealyticum induced a highly significant secretion of interleukin-1␤ (IL-1␤) and prostaglandin E 2 (PGE 2 ) by the amniochorion without changes in the extracellular matrix organization or content. These data demonstrate that group B streptococci induce degradation of the amniochorion as a result of MMP-9 production, probably via TNF-␣, whereas U. urealyticum stimulates the secretion of PGE 2 , probably via IL-1␤, potentially stimulating myometrial contraction. Our study provides novel evidence that the immunological cells circulating within the uterine microenvironment respond differentially to an infectious agent, triggering alternative molecular signaling pathways leading to human labor.

En route from artificial to natural: Evaluation of inhibitors of mannose-specific adhesion of E. coli under flow

“…Examples include harmful triggering of cellular signaling cascades, [1] invasion of host cells, [2] or biofilm formation. [3] One of the most common infectious diseases caused by bacterial adhesion are urinary tract A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 2 infections (UTI).…”

Intra-uterine experimental infection by Ureaplasma diversum induces TNF-α mediated womb inflammation in mice

“…These cytokines stimulate the secretion of other mediators, including prostaglandin E 2 and matrix metalloproteinases, which participate in the weakening of the fetal membranes and consequent disruption (Estrada-Gutierrez et al 2010).…”

Current Status of the Mollicute (Mycoplasma) Lung Disease: Pathogenesis, Diagnostics, Treatment and Prevention

“…The secretion of phospholipases A and C has been suggested to be the means by which ureaplasmas may initiate preterm labor by liberating arachidonic acid and altering prostaglandin synthesis (De Silva & Quinn, 1986). In addition, recently we reported that the interaction between U. urealyticum, intrauterine leukocytes and fetal membranes results in the secretion of high amounts of IL-1b and prostaglandin E2, which could induce uterine contraction leading to preterm labor (Estrada et al, 2010). Isolation of U. urealyticum from chorioamnion has been consistently associated with histological chorioamnionitis and is inversely related to birth weight, even when adjusting for duration of labor, rupture of the fetal membranes, and the presence of other bacteria [Cassel et al, 1993;.…”