scholarly journals Modulation of Death and Inflammatory Signaling in Decidual Stromal Cells following Exposure to Group B Streptococcus

2019 ◽  
Vol 87 (12) ◽  
Author(s):  
Rebecca A. Flaherty ◽  
Maja Magel ◽  
David M. Aronoff ◽  
Jennifer A. Gaddy ◽  
Margaret G. Petroff ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Inflammatory Responses ◽  
Severe Disease ◽  
Group B Streptococcus ◽  
Bacterial Pathogen ◽  
Mitogen Activated Protein Kinase ◽  
Antibody Microarray ◽  
Endometrial Stromal Cells ◽  
Decidual Tissue ◽  
Group B

ABSTRACT Group B Streptococcus (GBS) is an opportunistic bacterial pathogen that contributes to miscarriage, preterm birth, and serious neonatal infections. Studies have indicated that some multilocus sequence types (STs) of GBS are more likely to cause severe disease than others. We hypothesized that the ability of GBS to elicit varying host responses in maternal decidual tissue during pregnancy is an important factor regulating infection and disease severity. To address this hypothesis, we utilized an antibody microarray to compare changes in production and activation of host signaling proteins in decidualized telomerase-immortalized human endometrial stromal cells (dT-HESCs) following infection with GBS strains from septic neonates or colonized mothers. GBS infection increased levels of total and phosphorylated mitogen-activated protein kinase (MAPK) family members such as p38 and JNK and induced nuclear factor kappa B (NF-κB) pathway activation. Infection also altered the regulation of additional proteins that mediate cell death and inflammation in a strain-specific manner, which could be due to the observed variation in attachment to and invasion of the decidual stromal cells and ability to lyse red blood cells. Further analyses confirmed array results and revealed that p38 promotes programmed necrosis in dT-HESCs. Together, the observed signaling changes may contribute to deregulation of critical developmental signaling cascades and inflammatory responses following infection, both of which could trigger GBS-associated pregnancy complications.

Childhood meningitis in the conjugate vaccine era: a prospective cohort study

2014 ◽  
Vol 100 (3) ◽  
pp. 292-294 ◽  
Author(s):  
Manish Sadarangani ◽  
Louise Willis ◽  
Seilesh Kadambari ◽  
Stuart Gormley ◽  
Zoe Young ◽  
...  
Keyword(s):  
Bacterial Meningitis ◽  
Group B Streptococcus ◽  
Bacterial Pathogen ◽  
Antibiotic Use ◽  
Viral Meningitis ◽  
Older Children ◽  
C Reactive Protein ◽  
Blood Cell Count ◽  
Reactive Protein ◽  
Group B

Bacterial conjugate vaccines have dramatically changed the epidemiology of childhood meningitis; viral causes are increasingly predominant, but the current UK epidemiology is unknown. This prospective study recruited children under 16 years of age admitted to 3 UK hospitals with suspected meningitis. 70/388 children had meningitis—13 bacterial, 26 viral and 29 with no pathogen identified. Group B Streptococcus was the most common bacterial pathogen. Infants under 3 months of age with bacterial meningitis were more likely to have a reduced Glasgow Coma Score and respiratory distress than those with viral meningitis or other infections. There were no discriminatory clinical features in older children. Cerebrospinal fluid (CSF) white blood cell count and plasma C-reactive protein at all ages, and CSF protein in infants <3 months of age, distinguished between bacterial meningitis and viral meningitis or other infections. Improved diagnosis of non-bacterial meningitis is urgently needed to reduce antibiotic use and hospital stay.

Resveratrol suppresses inflammatory responses in endometrial stromal cells derived from endometriosis: A possible role of the sirtuin 1 pathway

2013 ◽  
Vol 40 (3) ◽  
pp. 770-778 ◽  
Author(s):  
Ayumi Taguchi ◽  
Osamu Wada-Hiraike ◽  
Kei Kawana ◽  
Kaori Koga ◽  
Aki Yamashita ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Inflammatory Responses ◽  
Sirtuin 1 ◽  
Endometrial Stromal Cells

scholarly journals Evidence of the Extrahepatic Replication of Hepatitis E Virus in Human Endometrial Stromal Cells

Pathogens ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 295 ◽  
Author(s):  
Mohamed A. El-Mokhtar ◽  
Essam R. Othman ◽  
Maha Y. Khashbah ◽  
Ali Ismael ◽  
Mohamed AA Ghaliony ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Stromal Cells ◽  
Hepatitis E Virus ◽  
Inflammatory Responses ◽  
Hepatitis E ◽  
Endometrial Stromal Cells ◽  
Extrahepatic Replication ◽  
Efficient Replication ◽  
Over Time

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. The tropism of HEV is not restricted to the liver, and the virus replicates in other organs. Not all the extrahepatic targets for HEV are identified. Herein, we found that non-decidualized primary human endometrial stromal cells (PHESCs), which are precursors for the decidua and placenta, are susceptible to HEV infection. PHESCs, isolated from healthy non-pregnant women (n = 5), were challenged with stool-derived HEV-1 and HEV-3. HEV RNA was measured by qPCR, and HEV capsid protein was assessed by flow cytometry, immunofluorescence (IF), and ELISA. HEV infection was successfully established in PHESCs. Intracellular and extracellular HEV RNA loads were increased over time, indicating efficient replication in vitro. In addition, HEV capsid protein was detected intracellularly in the HEV-infected PHESCs and accumulated extracellularly over time, confirming the viral assembly and release from the infected cells. HEV-1 replicated more efficiently in PHESCs than HEV-3 and induced more inflammatory responses. Ribavirin (RBV) treatment abolished the replication of HEV in PHESCs. In conclusion, PHESCs are permissive to HEV infection and these cells could be an endogenous source of HEV infection during pregnancy and mediate HEV vertical transmission.

scholarly journals USP10 promotes proliferation and migration and inhibits apoptosis of endometrial stromal cells in endometriosis through activating the Raf-1/MEK/ERK pathway

2018 ◽  
Vol 315 (6) ◽  
pp. C863-C872 ◽  
Author(s):  
Qiong Chen ◽  
Yuanyuan Hang ◽  
Tingting Zhang ◽  
Li Tan ◽  
Shuangdi Li ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Stromal Cells ◽  
Uterine Cavity ◽  
Mitogen Activated Protein Kinase ◽  
Erk Signaling ◽  
Erk Pathway ◽  
Endometrial Stromal Cells ◽  
And Migration ◽  
Proliferation And Migration

Endometriosis has been initially described as endometrial-like tissue outside of the uterine cavity. The mitogen-activated protein kinase/ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway playing an important role in the regulation of cell proliferation, apoptosis, and migration has been found to be activated in endometriosis. However, regulation of the MEK/ERK signaling pathway in endometriosis has not been fully understood. In this study, primary-cultured endometrial stromal cells were collected from patients with endometriosis and healthy controls, and the proliferation, apoptosis, and migration of ectopic endometrial stromal cells transfected with ubiquitin-specific protease 10 (USP10)-small-interfering RNA (siRNA) or pLVX-Puro-USP10 with or without MEK inhibitor PD-98059 or exogenous signaling stimulation such as epidermal growth factor (EGF) were measured by CCK-8, flow cytometry, and Transwell, respectively. The gene and protein expressions were measured by real-time PCR or Western blot. USP10 overexpression promoted ectopic endometrial stromal cell migration and proliferation, suppressed cell apoptosis, and activated MEK/ERK signaling that is a critical downstream target of the serine/threonine protein kinase Raf-1, which was significantly blocked by PD-98059. USP10 silencing demonstrated the inverse effects, and these effects induced by USP10 silencing were significantly blocked by EGF. USP10 overexpression promoted Raf-1 protein expression, but not mRNA expression, through deubiquitination. In conclusion, these results suggest that USP10 promotes proliferation and migration and inhibits apoptosis of endometrial stromal cells in endometriosis through activating the Raf-1/MEK/ERK pathway.

scholarly journals Group B Streptococcus Engages an Inhibitory Siglec through Sialic Acid Mimicry to Blunt Innate Immune and Inflammatory Responses In Vivo

2014 ◽  
Vol 10 (1) ◽  
pp. e1003846 ◽  
Author(s):  
Yung-Chi Chang ◽  
Joshua Olson ◽  
Federico C. Beasley ◽  
Christine Tung ◽  
Jiquan Zhang ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Inflammatory Responses ◽  
Group B Streptococcus ◽  
Innate Immune ◽  
Group B

Group B streptococcus isolates from septic patients and healthy carriers differentially activate platelet signaling cascades

2006 ◽  
Vol 95 (05) ◽  
pp. 836-849 ◽  
Author(s):  
Catharina Dornieden ◽  
Claudia Beyrich ◽  
Birgitta Schinke ◽  
Alexandra Schubert-Unkmeir ◽  
Marianne Abele-Horn ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Protein Kinase ◽  
Shape Change ◽  
Group B Streptococcus ◽  
Neonatal Morbidity ◽  
P38 Map Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Calcium Calmodulin Dependent ◽  
Group B ◽  
Platelet Thromboxane

SummaryInfection with group B streptococcus (GBS) is the most common cause of early onset neonatal sepsis in many countries, leading to neonatal morbidity and mortality.There is much evidence fora direct involvement of platelets in the pathogenesis of inflammation and sepsis. Several bacteria are known to directly interact with platelets leading to activation and aggregation,a phenomenon also observed with GBS. Here, we demonstrate that GBS rapidly bound to platelets; however, only strains isolated from septic patients bound fibrinogen on their surface and induced platelet thromboxane synthesis, platelet aggregation, and P-selectin (CD62P) expression. In contrast, GBS strains isolated from healthy newborns or healthy pregnant women induced only shape change, but not platelet thromboxane synthesis, platelet aggregation, or CD62P expression. All GBS strains investigated were able to activate FcγRIIA receptor signaling pathways including phospholipase C gamma2 (PLCγ2), as well as calcium/calmodulin-dependent myosin kinase II (CaMKII) and phosphorylation of myosin light chain (MLC). In contrast, protein kinase C (PKC) was exclusively activated by GBS strains isolated from septic patients, and p38 mitogen activated protein kinase (p38 MAP kinase) was preferentially activated by septic GBS strains. Furthermore, stress signaling kinase SEK1/MKK4 and focal adhesion kinase (FAK) were activated by all tested GBS strains in a FcγRIIA-independent way.This study demonstrates that septic, but not colonizing, GBS strains bind fibrinogen on their surface, and that septic GBS strains influence platelet function not only via the FcγRIIA receptor, but also via pathways distinct from IgG-mediated signalling. These mechanisms lead to platelet aggregation and secretion, thereby possibly modulating the pathophysiologic course of GBS infections.

scholarly journals Prevalence, serotype and antibiotic susceptibility of Group B Streptococcus isolated from pregnant women in Jakarta, Indonesia

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0252328
Author(s):  
Dodi Safari ◽  
Septiani Madonna Gultom ◽  
Wisnu Tafroji ◽  
Athiya Azzahidah ◽  
Frida Soesanti ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Antibiotic Susceptibility ◽  
Group B Streptococcus ◽  
Bacterial Pathogen ◽  
Neonatal Infection ◽  
Multidrug Resistant ◽  
Latex Agglutination ◽  
Antimicrobial Susceptibility Profile ◽  
Culture Identification ◽  
Group B

Group B Streptococcus (GBS) is a bacterial pathogen which is a leading cause of neonatal infection. Currently, there are limited GBS data available from the Indonesian population. In this study, GBS colonization, serotype distribution and antimicrobial susceptibility profile of isolates were investigated among pregnant women in Jakarta, Indonesia. Demographics data, clinical characteristics and vaginal swabs were collected from 177 pregnant women (mean aged: 28.7 years old) at 29–40 weeks of gestation. Bacterial culture identification tests and latex agglutination were performed for GBS. Serotyping was done by conventional multiplex PCR and antibiotic susceptibility testing by broth microdilution. GBS colonization was found in 53 (30%) pregnant women. Serotype II was the most common serotype (30%) followed by serotype III (23%), Ia and IV (13% each), VI (8%), Ib and V (6% each), and one non-typeable strain. All isolates were susceptible to vancomycin, penicillin, ampicillin, cefotaxime, daptomycin and linezolid. The majority of GBS were resistant to tetracycline (89%) followed by clindamycin (21%), erythromycin (19%), and levofloxacin (6%). The serotype III was more resistant to erythromycin, clindamycin, and levofloxacin and these isolates were more likely to be multidrug resistant (6 out of 10) compared to other serotypes. This report provides demographics of GBS colonization and isolate characterization in pregnant women in Indonesia. The results may facilitate preventive strategies to reduce neonatal GBS infection and improve its treatment.

scholarly journals Distinct Group B Streptococcus sequence and capsule types differentially impact macrophage stress and inflammatory signaling responses

2021 ◽  
Author(s):  
Rebecca A. Flaherty ◽  
David M. Aronoff ◽  
Jennifer A. Gaddy ◽  
Margaret G. Petroff ◽  
Shannon D. Manning
Keyword(s):  
Cell Death ◽  
Group B Streptococcus ◽  
Bacterial Pathogen ◽  
Distinct Group ◽  
Innate Immune Responses ◽  
Inflammatory Signaling ◽  
Phenotypic Differences ◽  
Pathway Activation ◽  
Nfκb Pathway ◽  
Group B

Group B Streptococcus (GBS) is an opportunistic bacterial pathogen that can contribute to the induction of preterm birth in colonized pregnant women and to severe neonatal disease. Many questions regarding the mechanisms that drive GBS-associated pathogenesis remain unanswered, and it is not yet clear why virulence has been observed to vary so extensively across GBS strains. Previously, we demonstrated that GBS strains of different sequence types (STs) and capsule (CPS) types induce different cytokine profiles in infected THP-1 macrophage-like cells. Here, we have expanded on these studies by utilizing the same set of genetically diverse GBS isolates to assess ST and CPS-specific differences in upstream cell death and inflammatory signaling pathways. Our results demonstrate that particularly virulent STs and CPS types, such as the ST-17 and CPS III groups, induce enhanced JNK and NFκB pathway activation following GBS infection of macrophages when compared with other ST or CPS groups. Additionally, we found that ST-17, CPS III and CPS V GBS strains induce the greatest levels of macrophage cell death during infection and exhibit a more pronounced ability to be internalized and to survive in macrophages following phagocytosis. These data provide further support for the hypothesis that variable host innate immune responses to GBS, which significantly impact pathogenesis, stem in part from genotypic and phenotypic differences among GBS isolates. These and similar studies may inform the development of improved diagnostic, preventive, or therapeutic strategies targeting invasive GBS infections.

scholarly journals CD82 gene suppression in endometrial stromal cells leads to increase of the cell invasiveness in the endometriotic milieu

2011 ◽  
Vol 47 (2) ◽  
pp. 195-208 ◽  
Author(s):  
Ming-Qing Li ◽  
Xiao-Fan Hou ◽  
Shi-Jian Lv ◽  
Yu-Han Meng ◽  
Xiao-Qiu Wang ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Wide Spectrum ◽  
Signal Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Metastasis Suppressor ◽  
Endometrial Stromal Cells ◽  
Protein Levels ◽  
Ectopic Tissue ◽  
Ccr2 Expression ◽  
Mitogen Activated Protein

Tetraspanin CD82 is a wide-spectrum tumor metastasis suppressor that inhibits motility and invasiveness of cancer cells. Endometriosis is a benign gynecological disorder, but appears malignant behaviors including invasion, ectopic implantation and recurrence. This study is to elucidate the role of CD82 expression regulation in the pathogenesis of endometriosis. The short interfering RNA silence was established to analyze the roles of CD82, chemokine CCL2, and its receptor CCR2 in the invasiveness of endometrial stromal cells (ESCs). We have found that the mRNA and protein levels of CD82 in the primary normal ESCs from endometrium without endometriosis are significantly higher than that of the primary ESCs from eutopic endometrium and ectopic tissue. CD82 inhibits the invasiveness of ESCs by downregulating CCL2 secretion and CCR2 expression via mitogen-activated protein kinase (MAPK) and integrinβ1 signal pathway, and in turn upregulating the expression of TIMP1 and TIMP2 in an autocrine manner. The combination of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) with 17β-estradiol can promote the invasion of ESCs via suppressing CD82 expression and stimulating CCL2 secretion and CCR2 expression, and the enhanced interaction of CCL2–CCR2 recruits more macrophages into the ectopic milieu in a paracrine manner, which further downregulates CD82 expression in the ectopic ESCs. Our study has demonstrated for the first time that the abnormal lower CD82 expression in ESCs induced by TCDD and estrogen may be an important molecular basis of endometriosis pathogenesis through enhancing the CCL2 secretion and CCR2 expression and the invasion of ESCs via MAPK and integrinβ1 signal pathway.

Sign in / Sign up

Export Citation Format

Share Document