Activation of the IL-1β/CXCL1/MMP-10 axis in chorioamnionitis induced by inactivated Group B Streptococcus

Bergeron, Julie; Gerges, Noha; Guiraut, Clémence; Grbic, Djordje; Allard, Marie-Julie; Fortier, Louis‐Charles; Vaillancourt, Cathy; Sébire, Guillaume

doi:10.1016/j.placenta.2016.09.016

Cited by 26 publications

(34 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inflammation-associated immune cell activation causes increased oxygen consumption and cellular respiration, so it is possible that the chorioamnionitis-exposed monocytes are upregulating hemoglobinassociated transcripts in an attempt to compensate for this [32]. Both term and preterm fetuses exposed to chorioamnionitis can mount a systemic inflammatory response, resulting in elevated fetal cortisol levels and fetal immune cell activation with increased expression of the cytokines and chemokines IL-1b, IL-6, TNF-a, G-CSF, and CXCL1 [33][34][35][36][37]. There is also an association between chorioamnionitis exposure and the development of early onset neonatal sepsis that persists even after adjusting for confounding factors such as birth weight and gestational age [38][39][40][41].…”

Section: Discussionmentioning

confidence: 99%

Chorioamnionitis exposure remodels the unique histone modification landscape of neonatal monocytes and alters the expression of immune pathway genes

et al. 2018

View full text Add to dashboard Cite

Chorioamnionitis is an intrauterine infection involving inflammation of the chorion, amnion and placenta. It leads to a fetal systemic inflammatory response that can alter the transcription of neonatal immune genes. We have previously shown that neonatal monocytes gain the activating histone tail modification H3K4me3 at promoters of immunologically important genes as development progresses from preterm neonate to adult. In this study, we applied ChIP-seq and RNA-seq to evaluate the impact of chorioamnionitis on the neonatal monocyte H3K4me3 histone modification landscape over the course of fetal and neonatal immune system development. Chorioamnionitis exposure in neonatal monocytes resulted in a net increase in total monocyte H3K4me3, primarily in introns and intergenic regions. Immune gene expression was decreased in chorioamnionitis-exposed monocytes, with the majority of enriched transcripts falling into pathways that are not linked to the immune system. Over half of all neonatal monocyte H3K4me3 peaks, independent of their location, were associated with active gene transcription. Overall, chorioamnionitis exposure resulted in global remodeling of the neonatal monocyte H3K4me3 landscape and changes in the expression of known immune genes. These changes resulted in a less robust inflammatory response upon exposure to a secondary challenge, which may explain why chorioamnionitis-exposed neonates have an increased risk of sepsis.

show abstract

Section: Discussionmentioning

confidence: 99%

Chorioamnionitis exposure remodels the unique histone modification landscape of neonatal monocytes and alters the expression of immune pathway genes

et al. 2018

View full text Add to dashboard Cite

show abstract

“…For example, in the SHR model, males – but not females – displayed hyperactivity during early puberty, but both sexes displayed increased levels of impulsivity and hyperactivity during adulthood (Bayless et al, 2015; Bergeron et al, 2013; van den Bergh et al, 2006). Distinct behavioral outcomes between males and females following end‐gestational GBS‐induced maternal immune activation might be consequences of sex‐specific inflammatory responses occurring during brain development (Allard et al, 2017; Bergeron et al, 2016). GBS‐exposed females presented a decreased thickness of the external capsule, a reduced periventricular myelin basic protein staining, oligodendrocyte maturation impairments, and a reduced density of microglial cells in the periventricular white matter (Bergeron et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Previous investigations documented sex‐specific placental inflammatory responses leading to placental and brain injuries, and subsequent autistic‐like behaviors in male rats in utero ‐exposed to live and inactivated serotype Ia GBS (Allard et al, 2017; Bergeron et al, 2016, 2013; Bucci et al, 2008; Rucklidge, 2010). Nevertheless, brain injuries were also present in female rats in utero ‐exposed to GBS‐induced inflammation (Bergeron et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Hyperactive behavior in female rats in utero‐exposed to group B Streptococcus‐induced inflammation

Allard

Brochu

Bergeron

et al. 2018

Intl J of Devlp Neuroscience

View full text Add to dashboard Cite

Group B Streptococcus (GBS) is one the most common bacterium responsible of maternal infections during pregnancy. Offspring in utero-exposed to GBS-induced placental inflammation displayed sex-specific forebrain injuries. Sex differences have been reported in several neuropsychiatric disorders. Hence, we hypothesized that female rats in utero-exposed to GBS may present sex-specific neurobehavioral impairments. Lewis rats were injected intraperitoneally every 12 h from gestational day (G) 19 to G22 with either saline (controls) or inactivated serotype Ia GBS (10 CFU). Before puberty, no difference in terms of spontaneous motor activity, exploratory or anxiety-related behaviors was noticed between experimental conditions. During puberty, GBS-exposed females - but not males - performed worse than same-sex controls in a forced motor task. During adulthood, GBS-exposed females - but not males - displayed increased spontaneous locomotor activity and decreased inhibition. In conclusion, our findings show for the first time that adult females - but not males - in utero-exposed to GBS-induced inflammation presented a hyperactive and disinhibited phenotype emerging after puberty.

show abstract

“…Cesarian (C)-sections were performed at G22 on two dams per experimental condition to confirm that GBSIa and GBSIII bacteria reached the placental tissue, inducing histological chorioamnionitis, as also described in our GBSIa rat model. 22 Pups born naturally were counted and weighed on P1 to prevent any stressful situation by handling dams on G23/P0. A total of six CTL litters and 14 GBSIII litters were used for behavioral testing (Fig.…”

Section: Experimental Designmentioning

confidence: 99%

“…[18][19][20] Using rat models of end-gestational active GBSIa infection and inactivated GBS-induced inflammation, we previously reported sex dichotomous effects in maternofetal inflammatory responses, chorioamnionitis and subsequent forebrain injuries as well as time-specific neurobehavioral impairments. [21][22][23] We hypothesized that end-gestational exposure to GBSIII will cause IUGR and CP-like neurobehavioral features. We based our experimental design on our established rat model of chorioamnionitis induced by killed GBSIa.…”

Section: Introductionmentioning

confidence: 99%

Causal role of group B Streptococcus-induced acute chorioamnionitis in intrauterine growth retardation and cerebral palsy-like impairments

Allard

Brochu

Bergeron

et al. 2019

J Dev Orig Health Dis

View full text Add to dashboard Cite

Chorioamnionitis and intrauterine growth retardation (IUGR) are risk factors for cerebral palsy (CP). Common bacteria isolated in chorioamnionitis include group B Streptococcus (GBS) serotypes Ia and III. Little is known about the impact of placental inflammation induced by different bacteria, including different GBS strains. We aimed to test the impact of chorioamnionitis induced by two common GBS serotypes (GBSIa and GBSIII) on growth and neuromotor outcomes in the progeny. Dams were exposed at the end of gestation to either saline, inactivated GBSIa or GBSIII. Inactivated GBS bacteria invaded placentas and triggered a chorioamnionitis featured by massive polymorphonuclear cell infiltrations. Offspring exposed to GBSIII – but not to GBSIa – developed IUGR, persisting beyond adolescent age. Male rats in utero exposed to GBSIII traveled a lower distance in the Open Field test, which was correlating with their level of IUGR. GBSIII-exposed rats presented decreased startle responses to acoustic stimuli beyond adolescent age. GBS-exposed rats displayed a dysmyelinated white matter in the corpus callosum adjacent to thinner primary motor cortices. A decreased density of microglial cells was detected in the mature corpus callosum of GBSIII-exposed males – but not females – which was correlating positively with the primary motor cortex thickness. Altogether, our results demonstrate a causal link between pathogen-induced acute chorioamnionitis and (1) IUGR, (2) serotype- and sex-specific neuromotor impairments and (3) abnormal development of primary motor cortices, dysmyelinated white matter and decreased density of microglial cells.

show abstract

Activation of the IL-1β/CXCL1/MMP-10 axis in chorioamnionitis induced by inactivated Group B Streptococcus

Cited by 26 publications

References 39 publications

Chorioamnionitis exposure remodels the unique histone modification landscape of neonatal monocytes and alters the expression of immune pathway genes

Chorioamnionitis exposure remodels the unique histone modification landscape of neonatal monocytes and alters the expression of immune pathway genes

Hyperactive behavior in female rats in utero‐exposed to group B Streptococcus‐induced inflammation

Causal role of group B Streptococcus-induced acute chorioamnionitis in intrauterine growth retardation and cerebral palsy-like impairments

Contact Info

Product

Resources

About