scholarly journals MyD88 Signaling Is Directly Involved in the Development of Murine Placental Malaria

2013 ◽  
Vol 82 (2) ◽  
pp. 830-838 ◽  
Author(s):  
Renato Barboza ◽  
Aramys Silva Reis ◽  
Leandro Gustavo da Silva ◽  
Lutero Hasenkamp ◽  
Keitty Raquel Benevides Pereira ◽  
...  
Keyword(s):  
Malaria Infection ◽  
Placental Malaria ◽  
Placental Tissue ◽  
Therapeutic Interventions ◽  
Histopathological Analysis ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Factor Alpha ◽  
Myd88 Signaling

ABSTRACTMalaria is a widespread infectious disease caused by the parasitePlasmodium. During pregnancy, malaria infection leads to a range of complications that can affect both the mother and fetus, including stillbirth, infant mortality, and low birth weight. In this study, we utilized a mouse model of placental malaria (PM) infection to determine the importance of the protein MyD88 in the host immune response toPlasmodiumduring pregnancy. Initially, we demonstrated thatPlasmodium bergheiNK65GFP adhered to placental tissue via chondroitin sulfate A and induced PM in mice with a C57BL/6 genetic background. To evaluate the involvement of MyD88 in the pathology of PM, we performed a histopathological analysis of placentas obtained from MyD88−/−and wild-type (WT) mice following infection on the 19th gestational day. Our data demonstrated that the detrimental placental alterations observed in the infected mice were correlated with the expression of MyD88. Moreover, in the absence of this protein, production of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) was significantly reduced in the infected mice. More importantly, in contrast to fetuses from infected WT mice, which exhibited a reduction in body weight, the fetuses from infected MyD88−/−mice did not display significant weight loss compared to their noninfected littermates. In addition, we observed a decrement of maternal care associated with malaria infection, which was attenuated in the MyD88-deficient mice. Collectively, the results of this study illustrate the pivotal importance of the MyD88 signaling pathway in the pathogenesis of placental malaria, thus presenting new possibilities for targeting MyD88 in therapeutic interventions.

scholarly journals Fusobacterium nucleatum Infection of Colonic Cells Stimulates MUC2 Mucin and Tumor Necrosis Factor Alpha

2011 ◽  
Vol 79 (7) ◽  
pp. 2597-2607 ◽  
Author(s):  
Poonam Dharmani ◽  
Jaclyn Strauss ◽  
Christian Ambrose ◽  
Emma Allen-Vercoe ◽  
Kris Chadee
Keyword(s):  
Tumor Necrosis ◽  
Bacterial Species ◽  
Fusobacterium Nucleatum ◽  
Mucin Secretion ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Factor Alpha ◽  
Colonic Cells ◽  
Necrosis Factor

ABSTRACTThe etiology of inflammatory bowel disease is not completely known, but it is influenced by the presence of normal gut microflora as well as yet-unrecognized pathogens. The anaerobic, Gram-negative bacterial speciesFusobacterium nucleatumis a common resident of the human mouth and gut and varies in its pathogenic potential. In this study, we demonstrate that highly invasiveF. nucleatumisolates derived from the inflamed guts of Crohn's disease patients evoked significantly greater MUC2 and tumor necrosis factor alpha (TNF-α) gene expression than minimally invasive strains isolated from the noninflamed gut in human colonic epithelial cells and in a rat ligated colonic loop model of infection. Only liveF. nucleatuminduced mucin secretion and TNF-α expression in direct contact with and/or during invasion of colonic cells. In rat colons, mucin secretion was augmented in response to a highly invasiveF. nucleatumisolate but was unaffected by treatment with a minimally invasive strain. Taken together, these studies reveal thatF. nucleatummay represent a challenging pathogen in the etiology of gut inflammatory diseases and highlight the importance of different pathotypes of candidate bacterial species in disease pathogenesis.

scholarly journals Enterococcus faecalisDemonstrates Pathogenicity through Increased Attachment in anEx VivoPolymicrobial Pulpal Infection

2018 ◽  
Vol 86 (5) ◽  
Author(s):  
Wayne Nishio Ayre ◽  
Genevieve Melling ◽  
Camille Cuveillier ◽  
Madhan Natarajan ◽  
Jessica L. Roberts ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Host Response ◽  
Ex Vivo ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Streptococcus Anginosus ◽  
Cell Counts ◽  
Tnf Α ◽  
Factor Alpha ◽  
Infection Types

ABSTRACTThis study investigated the host response to a polymicrobial pulpal infection consisting ofStreptococcus anginosusandEnterococcus faecalis, bacteria commonly implicated in dental abscesses and endodontic failure, using a validatedex vivorat tooth model. Tooth slices were inoculated with planktonic cultures ofS. anginosusorE. faecalisalone or in coculture atS. anginosus/E. faecalisratios of 50:50 and 90:10. Attachment was semiquantified by measuring the area covered by fluorescently labeled bacteria. Host response was established by viable histological cell counts, and inflammatory response was measured using reverse transcription-quantitative PCR (RT-qPCR) and immunohistochemistry. A significant reduction in cell viability was observed for single and polymicrobial infections, with no significant differences between infection types (∼2,000 cells/mm2for infected pulps compared to ∼4,000 cells/mm2for uninfected pulps).E. faecalisdemonstrated significantly higher levels of attachment (6.5%) thanS. anginosusalone (2.3%) and mixed-species infections (3.4% for 50:50 and 2.3% for 90:10), with a remarkable affinity for the pulpal vasculature. Infections withE. faecalisdemonstrated the greatest increase in tumor necrosis factor alpha (TNF-α) (47.1-fold forE. faecalis, 14.6-fold forS. anginosus, 60.1-fold for 50:50, and 25.0-fold for 90:10) and interleukin 1β (IL-1β) expression (54.8-fold forE. faecalis, 8.8-fold forS. anginosus, 54.5-fold for 50:50, and 39.9-fold for 90:10) compared to uninfected samples. Immunohistochemistry confirmed this, with the majority of inflammation localized to the pulpal vasculature and odontoblast regions. Interestingly,E. faecalissupernatant and heat-killedE. faecalistreatments were unable to induce the same inflammatory response, suggestingE. faecalispathogenicity in pulpitis is linked to its greater ability to attach to the pulpal vasculature.

scholarly journals Effects of MRP8, LPS, and Lenalidomide on the Expressions of TNF-α, Brain-Enriched, and Inflammation-Related MicroRNAs in the Primary Astrocyte Culture

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Ahmed Omran ◽  
Muhammad Usman Ashhab ◽  
Na Gan ◽  
Huimin Kong ◽  
Jing Peng ◽  
...  
Keyword(s):  
Therapeutic Interventions ◽  
Necrosis Factor Alpha ◽  
Small Noncoding Rnas ◽  
Primary Astrocyte ◽  
Tnf Α ◽  
Factor Alpha ◽  
Novel Target ◽  
First Time ◽  
Primary Astrocyte Culture ◽  
Necrosis Factor

Astrocytes are now recognized as a heterogeneous class of cells with many important and diverse functions in healthy and diseased central nervous system (CNS). MicroRNAs (miRNAs) are small, noncoding RNAs which may have key roles in astrocytes activation in response to various stimuli. We performed quantitative real-time PCR (qPCR) to detect changes in the expressions of brain-enriched miRNAs (124, 134, 9, 132, and 138), inflammation-related miRNAs (146a, 21, 181a, 221, and 222), and tumor necrosis factor alpha (TNF-α) in the rat primary astrocyte cultures after stimulation with myeloid-related protein 8 (MRP8) and lipopolysaccharides (LPS). Further, we inhibited the expression of TNF-αin the astrocytes by using TNF-αinhibitor (lenalidomide) and tested for the first time the effect of this inhibition on the expressions of the same tested miRNAs. Stimulation of the astrocytes with MRP8 or LPS leads to significant upregulation of miRNAs (124, 134, 9, 132, 146a, 21, 181a, 221, and 222), while miRNA-138 was downregulated. TNF-αinhibition with lenalidomide leads to opposite expressions of the tested miRNAs. These miRNAs may play an important role in activation of the astrocytes and may be a novel target for cell-specific therapeutic interventions in multiple CNS diseases.

scholarly journals Toll-Like Receptor 9 Is Required for Full Host Resistance toMycobacteriumaviumInfection but Plays No Role in Induction of Th1 Responses

2011 ◽  
Vol 79 (4) ◽  
pp. 1638-1646 ◽  
Author(s):  
Natália B. Carvalho ◽  
Fernanda S. Oliveira ◽  
Fernanda V. Durães ◽  
Leonardo A. de Almeida ◽  
Manuela Flórido ◽  
...  
Keyword(s):  
Interleukin 12 ◽  
Toll Like Receptor ◽  
Necrosis Factor Alpha ◽  
Histocompatibility Complex ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Myd88 Signaling ◽  
Necrosis Factor

ABSTRACTTo investigate the role of Toll-like receptor 9 (TLR9) in innate immunity toMycobacteriumavium, TLR9, TLR2, and MyD88 knockout (KO) mice were infected with this bacterium. Bacterial burdens were higher in the spleens, livers, and lungs of infected TLR9 KO mice than in those of C57BL/6 mice, indicating that TLR9 is required for efficient control ofM.aviuminfection. However, TLR9 KO or TLR2 KO spleen cells displayed normalM.avium-induced tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) responses. This finding was confirmed by determining the number of splenic CD4+T cells producing IFN-γ by flow cytometry. Furthermore, TLR2 and MyD88, but not TLR9, played a major role in interleukin-12 and TNF-α production byM.avium-infected macrophages and dendritic cells (DCs). We also found that major histocompatibility complex class II molecule expression on DCs is regulated by TLR2 and MyD88 signaling but not by TLR9. Finally, lack of TLR9, TLR2, or MyD88 reduced the numbers of macrophages, epithelioid cells, and lymphocytes inM.avium-induced granulomas but only MyD88 deficiency affected the number of liver granulomas. In summary, our data demonstrated that the involvement of TLR9 in the control ofM.aviuminfection is not related to the induction of Th1 responses.

scholarly journals Brucella abortus Invasion of Osteocytes Modulates Connexin 43 and Integrin Expression and Induces Osteoclastogenesis via Receptor Activator of NF-κB Ligand and Tumor Necrosis Factor Alpha Secretion

2015 ◽  
Vol 84 (1) ◽  
pp. 11-20 ◽  
Author(s):  
Ayelén Ivana Pesce Viglietti ◽  
Paula Constanza Arriola Benitez ◽  
María Virginia Gentilini ◽  
Lis Noelia Velásquez ◽  
Carlos Alberto Fossati ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Brucella Abortus ◽  
Connexin 43 ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Receptor Activator ◽  
Factor Alpha ◽  
Necrosis Factor

Osteoarticular brucellosis is the most common localization of human active disease. Osteocytes are the most abundant cells of bone. They secrete factors that regulate the differentiation of both osteoblasts and osteoclasts during bone remodeling. The aim of this study is to determine ifBrucella abortusinfection modifies osteocyte function. Our results indicate thatB. abortusinfection induced matrix metalloproteinase 2 (MMP-2), receptor activator for NF-κB ligand (RANKL), proinflammatory cytokines, and keratinocyte chemoattractant (KC) secretion by osteocytes. In addition, supernatants fromB. abortus-infected osteocytes induced bone marrow-derived monocytes (BMM) to undergo osteoclastogenesis. Using neutralizing antibodies against tumor necrosis factor alpha (TNF-α) or osteoprotegerin (OPG), RANKL's decoy receptor, we determined that TNF-α and RANKL are involved in osteoclastogenesis induced by supernatants fromB. abortus-infected osteocytes. Connexin 43 (Cx43) and the integrins E11/gp38, integrin-α, integrin-β, and CD44 are involved in cell-cell interactions necessary for osteocyte survival.B. abortusinfection inhibited the expression of Cx43 but did not modify the expression of integrins. Yet the expression of both Cx43 and integrins was inhibited by supernatants fromB. abortus-infected macrophages.B. abortusinfection was not capable of inducing osteocyte apoptosis. However, supernatants fromB. abortus-infected macrophages induced osteocyte apoptosis in a dose-dependent manner. Taken together, our results indicate thatB. abortusinfection could alter osteocyte function, contributing to bone damage.

scholarly journals Inhibition of the NF-κB Pathway in Human Intestinal Epithelial Cells by Commensal Streptococcus salivarius

2011 ◽  
Vol 77 (13) ◽  
pp. 4681-4684 ◽  
Author(s):  
Ghalia Kaci ◽  
Omar Lakhdari ◽  
Joël Doré ◽  
S. Dusko Ehrlich ◽  
Pierre Renault ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Streptococcus Salivarius ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Human Intestinal Epithelial Cells ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACTStreptococcus salivariusexhibited an anti-inflammatory effect on intestinal epithelial cells (IECs) and monocytes. Strains were screened using a reporter clone, HT-29/kB-luc-E, induced by tumor necrosis factor alpha (TNF-α). Supernatant from each strain downregulated NF-κB activation. The two most efficient strains produced an active metabolite (<3 kDa) which was able to downregulate the secretion of the proinflammatory chemokine interleukin-8 (IL-8).

scholarly journals Haemophilus ducreyi Lipooligosaccharides Induce Expression of the Immunosuppressive Enzyme Indoleamine 2,3-Dioxygenase via Type I Interferons and Tumor Necrosis Factor Alpha in Human Dendritic Cells

2011 ◽  
Vol 79 (8) ◽  
pp. 3338-3347 ◽  
Author(s):  
Wei Li ◽  
Barry P. Katz ◽  
Stanley M. Spinola
Keyword(s):  
Dendritic Cells ◽  
Tumor Necrosis ◽  
Treg Cells ◽  
Type I Interferons ◽  
Type I ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACTHaemophilus ducreyicauses chancroid, a genital ulcer disease. In human inoculation experiments, most volunteers fail to clear the bacteria despite the infiltration of innate and adaptive immune cells to the infected sites. The immunosuppressive protein indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme in thel-tryptophan-kynurenine metabolic pathway. Tryptophan depletion and tryptophan metabolites contribute to pathogen persistence by inhibiting T cell proliferation, inducing T cell apoptosis, and promoting the expansion of FOXP3+regulatory T (Treg) cells. We previously found that FOXP3+Treg cells are enriched in experimental lesions and thatH. ducreyiinduced IDO transcription in dendritic cells (DC) derived from blood of infected volunteers who developed pustules. Here, we showed that enzymatically active IDO was induced in DC byH. ducreyi. Neutralizing antibodies against interferon alpha/beta receptor 2 chain (IFNAR2) and tumor necrosis factor alpha (TNF-α) inhibited IDO induction. Inhibitors of the mitogen-activated protein kinase (MAPK) p38 and nuclear factor-κB (NF-κB) also inhibited IDO expression. Neither bacterial contact with nor uptake by DC was required for IDO activation.H. ducreyiculture supernatant andH. ducreyilipooligosaccharides (LOS) induced IDO expression, which required type I interferons, TNF-α, and the three MAPK (p38, c-Jun N-terminal kinase, and extracellular signal regulated kinase) and NF-κB pathways. In addition, LOS-induced IFN-β activated the JAK-STAT pathway. Blocking the LOS/Toll-like receptor 4 (TLR4) signaling pathway greatly reducedH. ducreyi-induced IDO production. These findings indicate thatH. ducreyi-induced IDO expression in DC is largely mediated by LOS via type I interferon- and TNF-α-dependent mechanisms and the MAPK, NF-κB, and JAK-STAT pathways.

scholarly journals Interleukin 17 Receptor E (IL-17RE) and IL-17C Mediate the Recruitment of Neutrophils during Acute Streptococcus pneumoniae Pneumonia

2019 ◽  
Vol 87 (11) ◽  
Author(s):  
Patrick Steck ◽  
Felix Ritzmann ◽  
Anja Honecker ◽  
Giovanna Vella ◽  
Christian Herr ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Alveolar Macrophages ◽  
Pulmonary Inflammation ◽  
Interleukin 17 ◽  
Immune Functions ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Factor Alpha ◽  
Functional Receptor

ABSTRACT Neutrophils contribute to lung injury in acute pneumococcal pneumonia. The interleukin 17 receptor E (IL-17RE) is the functional receptor for the epithelial-derived cytokine IL-17C, which is known to mediate innate immune functions. The aim of this study was to investigate the contribution of IL-17RE/IL-17C to pulmonary inflammation in a mouse model of acute Streptococcus pneumoniae pneumonia. Numbers of neutrophils and the expression levels of the cytokine granulocyte colony-stimulating factor (G-CSF) and tumor necrosis factor alpha (TNF-α) were decreased in lungs of IL-17RE-deficient (Il-17re−/−) mice infected with S. pneumoniae. Numbers of alveolar macrophages rapidly declined in both wild-type (WT) and Il-17re−/− mice and recovered 72 h after infection. There were no clear differences in the elimination of bacteria and numbers of blood granulocytes between infected WT and Il-17re−/− mice. The fractions of granulocyte-monocyte progenitors (GMPs) were significantly reduced in infected Il-17re−/− mice. Numbers of neutrophils were significantly reduced in lungs of mice deficient for IL-17C 24 h after infection with S. pneumoniae. These data indicate that the IL-17C/IL-17RE axis promotes the recruitment of neutrophils without affecting the recovery of alveolar macrophages in the acute phase of S. pneumoniae lung infection.

scholarly journals NF-κB RelA Is Required for Hepatoprotection during Pneumonia and Sepsis

2019 ◽  
Vol 87 (8) ◽  
Author(s):  
Yuri Kim ◽  
Eri Allen ◽  
Lillia A. Baird ◽  
Elise M. Symer ◽  
Filiz T. Korkmaz ◽  
...  
Keyword(s):  
Liver Injury ◽  
Acute Phase ◽  
Cell Activation ◽  
Phase Changes ◽  
Nkt Cell ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Factor Alpha ◽  
Hepatic Transcriptome

ABSTRACT Pneumonia and sepsis are distinct but integrally linked public health concerns. The hepatic acute-phase response (APR), which is largely dependent on transcription factors NF-κB RelA and STAT3, is a hallmark of these pathologies and other injurious conditions. Inactivation of the APR can promote liver injury, a frequently observed organ dysfunction during sepsis. However, whether or how the acute-phase changes promote liver tissue resilience during infections is unclear. To determine the hepatoprotective role of the hepatic APR, we utilized mice bearing hepatocyte-specific deletions of either RelA or STAT3. Mice were challenged intratracheally (i.t.), intravenously (i.v.), or intraperitoneally (i.p.) with Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, lipopolysaccharide (LPS), or alpha-galactosylceramide (αGalCer) to induce pneumonia, sepsis, or NKT cell activation. Liver injury was observed in RelA-null (hepRelAΔ/Δ) mice but not STAT3-null (hepSTAT3Δ/Δ) mice during pneumonia. The absence of RelA resulted in hepatotoxicity across several models of pneumonia, sepsis, and NKT cell activation. Injury was associated with increased levels of activated caspase-3 and -8 and substantial alteration of the hepatic transcriptome. Hepatotoxicity in the absence of RelA could be reversed by neutralization of tumor necrosis factor alpha (TNF-α). These results indicate the requirement of RelA-dependent inducible hepatoprotection during pneumonia and sepsis. Further, the results demonstrate that RelA-dependent gene programs are critical for maintaining liver homeostasis against TNF-α-driven immunotoxicity.

scholarly journals CXC Ligand 9 Response to Malaria during Pregnancy Is Associated with Low-Birth-Weight Deliveries

2012 ◽  
Vol 80 (9) ◽  
pp. 3034-3038 ◽  
Author(s):  
Shu Dong ◽  
Jonathan D. Kurtis ◽  
Sunthorn Pond-Tor ◽  
Edward Kabyemela ◽  
Patrick E. Duffy ◽  
...  
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Strong Association ◽  
Placental Malaria ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Malaria During Pregnancy ◽  
Placental Blood ◽  
Ifn Γ

ABSTRACTPlacental infection withPlasmodium falciparumis associated with increased levels of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ), and previous studies have associated increased levels of these cytokines with low birth weight (LBW), especially for malaria-infected primigravidae. To define the contribution of TNF-α and IFN-γ networks to placental-malaria-associated LBW, we measured chemokines induced by TNF-α and IFN-γ and related them to birth weight in a birth cohort of 782 mother-infant pairs residing in an area ofP. falciparumholoendemicity in Tanzania. Among primigravidae, levels of CCL2, CXC ligand 9 (CXCL9), and CXCL13 were significantly higher during malaria infection in both the placenta and peripheral blood. Placental CXCL9 and CXCL13 levels were also higher in placental blood from secundigravidae and multigravidae. In multivariate analyses adjusted for known predictors of birth weight, malaria-infected primigravidae with placental CXCL9 levels in the lowest tertile gave birth to babies who weighed 610 g more than babies born to mothers with high CXCL9 levels. CXCL9 expression is induced by IFN-γ, and the strong association between birth weight and placental CXCL9 is consistent with previous observations relating IFN-γ to poor pregnancy outcomes.

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