TNF-Signaling Modulates Neutrophil-Mediated Immunity at the Feto-Maternal Interface During LPS-Induced Intrauterine Inflammation.

Accumulation of activated neutrophils at the feto-maternal interface is a defining hallmark of intrauterine inflammation (IUI) that might trigger an excessive immune response during pregnancy. Mechanisms responsible of this massive neutrophil recruitment are poorly investigated. We have previously showed that intraamniotic injection of LPS in rhesus macaques induced a neutrophil predominant inflammatory response similar to that seen in human IUI.

Intraamniotic Zika virus inoculation of pregnant rhesus macaques produces fetal neurologic disease.

Zika virus (ZIKV) infection of pregnant women can cause fetal microcephaly and other neurologic defects. We describe the development of a non-human primate model to better understand fetal pathogenesis. To reliably induce fetal infection at defined times, four pregnant rhesus macaques are inoculated intravenously and intraamniotically with ZIKV at gestational day (GD) 41, 50, 64, or 90, corresponding to first and second trimester of gestation.

IL-1 signaling mediates intrauterine inflammation and chorio-decidua neutrophil recruitment and activation.

Neutrophil infiltration of the chorioamnion-decidua tissue at the maternal-fetal interface (chorioamnionitis) is a leading cause of prematurity, fetal inflammation, and perinatal mortality. We induced chorioamnionitis in preterm rhesus macaques by intraamniotic injection of LPS. Here, we show that, during chorioamnionitis, the amnion upregulated phospho-IRAK1-expressed neutrophil chemoattractants CXCL8 and CSF3 in an IL-1-dependent manner.

Extremely preterm fetal sheep lung responses to antenatal steroids and inflammation.

Background: The efficacy of antenatal steroids for fetal lung maturation in the periviable period is not fully understood.

Objective: We sought to determine the lung maturational effects of antenatal steroids and inflammation in early gestation sheep fetuses, similar to the periviable period in human beings.

Study Design: Date-mated ewes with singleton fetuses were randomly assigned to 1 of 4 treatment groups (n = 8/group): (1) maternal intramuscular injection of betamethasone; (2) intraamniotic lipopolysaccharide; (3) betamethasone + lipopolysaccharide; and (4) intraamniotic + intramuscular saline (controls).

Intra-amniotic Ureaplasma parvum-Induced Maternal and Fetal Inflammation and Immune Responses in Rhesus Macaques.

Background: Although Ureaplasma species are the most common organisms associated with prematurity, their effects on the maternal and fetal immune system remain poorly characterized.

Methods: Rhesus macaque dams at approximately 80% gestation were injected intra-amniotically with 10 colony-forming units of Ureaplasma parvum or saline (control). Fetuses were delivered surgically 3 or 7 days later.

Neutrophil recruitment and activation in decidua with intra-amniotic IL-1beta in the preterm rhesus macaque.

Chorioamnionitis, an infection/inflammation of the fetomaternal membranes, is frequently associated with preterm delivery. The mechanisms of inflammation in chorioamnionitis are poorly understood. We hypothesized that neutrophils recruited to the decidua would be the major producers of proinflammatory cytokines.

Chorioamnionitis-induced fetal gut injury is mediated by direct gut exposure of inflammatory mediators or by lung inflammation.

Intra-amniotic exposure to proinflammatory agonists causes chorioamnionitis and fetal gut inflammation. Fetal gut inflammation is associated with mucosal injury and impaired gut development. We tested whether this detrimental inflammatory response of the fetal gut results from a direct local (gut derived) or an indirect inflammatory response mediated by the chorioamnion/skin or lung, since these organs are also in direct contact with the amniotic fluid.

ChiS histidine kinase negatively regulates the production of chitinase ChiC in Streptomyces peucetius.

Computational analysis of sequence homology of the chiSRC gene cluster, encoding a chitinase in Streptomyces peucetius, showed that the gene cluster could be a two-component regulon comprising a sensor kinase (chiS) and a response regulator (chiR). To prove that the ChiSRC is an authentic two-component system, the chiS gene was cloned and expressed in E.coli and the purified protein was used for biochemical analysis.

Intra-amniotic IL-1β induces fetal inflammation in rhesus monkeys and alters the regulatory T cell/IL-17 balance.

Very low birth weight preterm newborns are susceptible to the development of debilitating inflammatory diseases, many of which are associated with chorioamnionitis. To define the effects of chorioamnionitis on the fetal immune system, IL-1β was administered intra-amniotically at ~80% gestation in rhesus monkeys. IL-1β caused histological chorioamnionitis, as well as lung inflammation (infiltration of neutrophils or monocytes in the fetal airways).

Repeated exposure to intra-amniotic LPS partially protects against adverse effects of intravenous LPS in preterm lambs.

Histologic chorioamnionitis, frequently associated with preterm births and adverse outcomes, results in prolonged exposure of preterm fetuses to infectious agents and pro-inflammatory mediators, such as LPS. Endotoxin tolerance-type effects were demonstrated in fetal sheep following repetitive systemic or intra-amniotic (i.a.

Identification of maternally regulated fetal gene networks in the placenta with a novel embryo transfer system in mice.

The mechanisms for provisioning maternal resources to offspring in placental mammals involve complex interactions between maternally regulated and fetally regulated gene networks in the placenta, a tissue that is derived from the zygote and therefore of fetal origin. Here we describe a novel use of an embryo transfer system in mice to identify gene networks in the placenta that are regulated by the mother. Mouse embryos from the same strain of inbred mice were transferred into a surrogate mother either of the same strain or from a different strain, allowing maternal and fetal effects on the placenta to be separated.

Intergeneric conjugation in Streptomyces peucetius and Streptomyces sp. strain C5: chromosomal integration and expression of recombinant plasmids carrying the chiC gene.

Intergeneric conjugal transfer of plasmid DNA from Escherichia coli to Streptomyces circumvents problems such as host-controlled restriction and instability of foreign DNA during the transformation of Streptomyces protoplasts. The anthracycline antibiotic-producing strains Streptomyces peucetius and Streptomyces sp. strain C5 were transformed using E.