scholarly journals Microneme Proteins 1 and 4 From Toxoplasma gondii Induce IL-10 Production by Macrophages Through TLR4 Endocytosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Rafael Ricci-Azevedo ◽  
Flavia Costa Mendonça-Natividade ◽  
Ana Carolina Santana ◽  
Juliana Alcoforado Diniz ◽  
Maria Cristina Roque-Barreira
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Inflammatory Cytokine ◽  
Early Stage ◽  
Protozoan Parasite ◽  
Cell Responses ◽  
Tnf Α ◽  
Host Inflammatory Response ◽  
Anti Inflammatory Cytokine ◽  
Microneme Proteins

The protozoan parasite Toxoplasma gondii modulates host cell responses to favor its success in the early stage of infections by secreting proteins from its apical organelles. Some of these proteins, including microneme proteins (MICs) 1 and 4, trigger pro-inflammatory host cell responses. The lectins MIC1 and MIC4 interact with N-linked glycans on TLR2 and TLR4, activating NF-κB and producing IL-12, TNF-α, and IL-6. Interestingly, MIC1 and MIC4 also trigger secretion of the anti-inflammatory cytokine IL-10 through mechanisms as yet unknown. Herein, we show that the ability of these MICs to induce macrophages to produce IL-10 depends on TLR4 internalization from the cell surface. Macrophages subjected to blockade of endocytosis by Dynasore continued to release TNF-α, but failed to produce IL-10, in response to MIC1 or MIC4 exposure. Similarly, IL-10 was not produced by Dynasore-conditioned T. gondii-infected macrophages. Furthermore, MIC1- or MIC4-stimulated macrophages gained transient tolerance to LPS. We report a previously undiscovered mechanism by which well-defined T. gondii components inhibit a host inflammatory response.

Association of host cell endoplasmic reticulum and mitochondria with the Toxoplasma gondii parasitophorous vacuole membrane: a high affinity interaction

1997 ◽  
Vol 110 (17) ◽  
pp. 2117-2128 ◽  
Author(s):  
A.P. Sinai ◽  
P. Webster ◽  
K.A. Joiner
Keyword(s):  
Endoplasmic Reticulum ◽  
Toxoplasma Gondii ◽  
Host Cell ◽  
Parasitophorous Vacuole ◽  
Protozoan Parasite ◽  
Host Cells ◽  
Parasitophorous Vacuole Membrane ◽  
Vacuole Membrane ◽  
Protein Protein Interaction ◽  
High Affinity

The parasitophorous vacuole membrane (PVM) of the obligate intracellular protozoan parasite Toxoplasma gondii forms tight associations with host mitochondria and the endoplasmic reticulum (ER). We have used a combination of morphometric and biochemical approaches to characterize this unique phenomenon, which we term PVM-organelle association. The PVM is separated from associated mitochondria and ER by a mean distance of 12 and 18 nm, respectively. The establishment of PVM-organelle association is dependent on active parasite entry, but does not require parasite viability for its maintenance. Association is not a consequence of spatial constraints imposed on the growing vacuole. Morphometric analysis indicates that the extent of mitochondrial association with the PVM stays constant as the vacuole enlarges, whereas the extent of ER association decreases. Disruption of host cell microtubules partially blocks the establishment but not the maintenance of PVM-mitochondrial association, and has no significant effect on PVM-ER association. PVM-organelle association is maintained following disruption of infected host cells, as assessed by electron microscopy and by sub-cellular fractionation showing co-migration of fixed PVM and organelle markers. Taken together, the data suggest that a high affinity, potentially protein-protein interaction between parasite and organelle components is responsible for PVM-organelle association.

scholarly journals P0527AROLE OF PROMOTING INFLAMMATION OF KLF6 IN ACUTE KIDNEY INURY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Dan Li ◽  
Chenyu Li ◽  
Yan Xu
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tnf Α ◽  
Public Dataset ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine ◽  
Pro Inflammatory Cytokines

Abstract Background and Aims Acute kidney injury (AKI), commonly appeared in cardiac arrest, surgery and kidney transplantation which involved in ischemia-reperfusion (IR) injury of kidney. However, the mechanisms underlying inflammatory response in IR AKI is still unclear. Method Public dataset showed kruppel-like factor 6 (KLF6) was significantly highly expressed (P<0.05) in AKI, implies KLF6 might be associated with AKI. To evaluate the mechanism of KLF6 on IR AKI, 30 rats were randomly divided into sham and IR group, and were sacrificed at 0 h, 3 h, 6 h, 12 h or 24 h after IR. Results The results showed KLF6 expression was peaking at 6 h after IR, and the expression of pro-inflammatory cytokines MCP-1 and TNF-α were increased both in serum and kidney tissues after IR, while anti-inflammatory cytokine IL-10 was decreased after IR. Furthermore, in vitro results showed KLF6 knock-down reduced the pro-inflammatory cytokines expression and increased the anti-inflammatory cytokines expression. Conclusion These results suggest that (1) KLF6 might be a novel biomarker for early diagnosis of AKI and (2) targeting KLF6 expression may offer novel strategies to protect kidneys from IR AKI Figure KLF6, AKI, Control Inflammation

scholarly journals The Protozoan Parasite Toxoplasma gondii Selectively Reprograms the Host Cell Translatome

2018 ◽  
Vol 86 (9) ◽  
Author(s):  
Louis-Philippe Leroux ◽  
Julie Lorent ◽  
Tyson E. Graber ◽  
Visnu Chaparro ◽  
Laia Masvidal ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Cell Activation ◽  
Immune Cell ◽  
Mrna Translation ◽  
Protozoan Parasite ◽  
Translational Efficiency ◽  
Type I ◽  
Content Type ◽  
Infection Inhibition

ABSTRACT The intracellular parasite Toxoplasma gondii promotes infection by targeting multiple host cell processes; however, whether it modulates mRNA translation is currently unknown. Here, we show that infection of primary murine macrophages with type I or II T. gondii strains causes a profound perturbation of the host cell translatome. Notably, translation of transcripts encoding proteins involved in metabolic activity and components of the translation machinery was activated upon infection. In contrast, the translational efficiency of mRNAs related to immune cell activation and cytoskeleton/cytoplasm organization was largely suppressed. Mechanistically, T. gondii bolstered mechanistic target of rapamycin (mTOR) signaling to selectively activate the translation of mTOR-sensitive mRNAs, including those with a 5′-terminal oligopyrimidine (5′ TOP) motif and those encoding mitochondrion-related proteins. Consistent with parasite modulation of host mTOR-sensitive translation to promote infection, inhibition of mTOR activity suppressed T. gondii replication. Thus, selective reprogramming of host mRNA translation represents an important subversion strategy during T. gondii infection.

scholarly journals Hyperbaric oxygen enhances neutrophil apoptosis and their clearance by monocyte-derived macrophages

2015 ◽  
Vol 93 (4) ◽  
pp. 405-416 ◽  
Author(s):  
Anwar J. Almzaiel ◽  
Richard Billington ◽  
Gary Smerdon ◽  
A. John Moody
Keyword(s):  
Mrna Expression ◽  
Hyperbaric Oxygen ◽  
Inflammatory Cytokine ◽  
Cytokine Gene Expression ◽  
Neutrophil Apoptosis ◽  
Normobaric Hyperoxia ◽  
Tnf Α ◽  
Pre Treatment ◽  
Bovine Neutrophils ◽  
Anti Inflammatory Cytokine

Neutrophil apoptosis and clearance by macrophages are essential for wound healing. Evidence suggests that hyperbaric oxygen (HBO) exposure may enhance neutrophil apoptosis, but HBO effects leading to neutrophil clearance by macrophages are still unclear. In the current study, bovine neutrophils and monocyte-derived macrophages (MDMΦ) were co-cultured under HBO (97.9% O2, 2.1% CO2 at 2.4 atm absolute (ATA)) (1 atm = 101.325 kPa), hyperbaric normoxia (8.8% O2 at 2.4 ATA), normobaric hyperoxia (95% O2, 5% CO2), normoxia (air), and normobaric hypoxia (5% O2, 5% CO2). Phagocytosis of fresh and 22 h aged neutrophils by MDMΦ was increased after HBO pre-treatment, assessed using flow cytometry and light microscopy. Enhanced clearance of neutrophils was accompanied by an increase in H2O2 levels following HBO pre-treatment with upregulation of IL-10 (anti-inflammatory cytokine) mRNA expression in LPS-stimulated MDMΦ that had ingested aged neutrophils. TNF-α (pro-inflammatory cytokine) gene expression did not change in LPS-stimulated MDMΦ that had ingested fresh or aged neutrophils after HBO, pressure, and hyperoxia. These findings suggest that HBO-activated MDMΦ participate in the clearance of apoptotic cells. Uptake of neutrophils by MDMΦ exposed to HBO may contribute to resolution of inflammation, because HBO induced up-regulation of IL-10 mRNA expression.

scholarly journals Host Cell Invasion by Toxoplasma gondii Is Temporally Regulated by the Host Microtubule Cytoskeleton

2010 ◽  
Vol 9 (11) ◽  
pp. 1680-1689 ◽  
Author(s):  
Kristin R. Sweeney ◽  
Naomi S. Morrissette ◽  
Stephanie LaChapelle ◽  
Ira J. Blader
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Viral Infections ◽  
Protozoan Parasite ◽  
Host Cells ◽  
Cell Tropism ◽  
Microtubule Cytoskeleton ◽  
Parasite Invasion ◽  
Content Type ◽  
Microtubule Disruption

ABSTRACT Toxoplasma gondii is an obligate intracellular protozoan parasite that invades and replicates within most nucleated cells of warm-blooded animals. The basis for this wide host cell tropism is unknown but could be because parasites invade host cells using distinct pathways and/or repertoires of host factors. Using synchronized parasite invasion assays, we found that host microtubule disruption significantly reduces parasite invasion into host cells early after stimulating parasite invasion but not at later time points. Host microtubules are specifically associated with the moving junction, which is the site of contact between the host cell and the invading parasite. Host microtubules are specifically associated with the moving junction of those parasites invading early after stimulating invasion but not with those invading later. Disruption of host microtubules has no effect on parasite contact, attachment, motility, or rate of penetration. Rather, host microtubules hasten the time before parasites commence invasion. This effect on parasite invasion is distinct from the role that host microtubules play in bacterial and viral infections, where they function to traffic the pathogen or pathogen-derived material from the host cell's periphery to its interior. These data indicate that the host microtubule cytoskeleton is a structure used by Toxoplasma to rapidly infect its host cell and highlight a novel function for host microtubules in microbial pathogenesis.

scholarly journals Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition

2020 ◽  
Author(s):  
Christian Rodriguez Rodrigues ◽  
María Celeste Nicolao ◽  
Maia Chop ◽  
Natalia Plá ◽  
Mora Massaro ◽  
...  
Keyword(s):  
Echinococcus Granulosus ◽  
Innate Immune ◽  
Antigen Uptake ◽  
Mhc Ii ◽  
Cell Functions ◽  
Cell Responses ◽  
Tnf Α ◽  
First Time ◽  
Priming Activity ◽  
Anti Inflammatory Cytokine

1.AbstractImmune evasion is a hallmark of persistent echinococcal infection, comprising modulation of innate immune cells and antigen-specific T cell responses. However, recognition of Echinococcus granulosus by dendritic cells (DCs) is a key determinant of the host’s response to this parasite. Given that mTOR signaling pathway has been described as a regulator linking metabolism and immune function in DCs, we reported for the first time in these cells, global translation levels, antigen uptake, phenotype, cytokine transcriptional levels, and splenocyte priming activity upon recognition of the hydatid fluid (HF) and the highly glycosylated laminar layer (LL). We found that LL induced a slight up-regulation of CD86 and MHC II in DCs and also stimulated the production of IL-6 and TNF-α. By contrast, HF did not increase the expression of any co-stimulatory molecules, but also down-modulated CD40 and stimulated the expression of the anti-inflammatory cytokine IL-10. Both parasitic antigens promoted protein synthesis through mTOR activation. The use of rapamycin decreased the expression of the cytokines tested, empowered the down-modulation of CD40 and also reduced splenocyte proliferation. Finally, we showed that E. granulosus antigens increase the amounts of LC3-positive structures in DCs which play critical roles in the presentation of these antigens to T cells.

scholarly journals Pro- and Anti-Inflammatory Cytokine Expression Levels in Macrophages; An Approach to Develop Indazolpyridin-methanones as Novel Inflammation Medication

2020 ◽  
Vol 19 (4) ◽  
pp. 425-435 ◽  
Author(s):  
Manikandan Alagumuthu ◽  
Vanshika Srivastava ◽  
Manisha Shah ◽  
Sivakumar Arumugam ◽  
Mohandoss Sonaimuthu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Inflammatory Cytokine ◽  
Cancer Cell Lines ◽  
Tnf Α ◽  
Anti Cancer ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine

Background: Macrophages play a serious part in the instigation, upkeep, and resolution of inflammation. They are activated or deactivated during inflammation progression. Activation signals include cytokines (IF-γ, granulocyte-monocyte colonystimulating factor (GM-CSF), and TNF-α), extracellular matrix proteins, and other chemical mediators. Activated macrophages are deactivated by anti-inflammatory cytokines (IL- 10 and TGF-β (transforming growth factor-beta) and cytokine antagonists that are mainly produced by macrophages. Based on this, the present study aimed to develop novel (E)- Benzylidene-indazolpyridin methanones (Cpd-1-10) as effective anti-inflammatory agents by analyzing pro- and anti-inflammatory cytokine levels in macrophages. Objectives: To determine the anti-inflammatory effect of indazolpyridin-methanones by examining pro- and anti-inflammatory interleukin levels in J77A.1 macrophages. Methods: Expression of cytokines such as TNF-α, IL-1β, IL-6 and IL-10 serum levels measured by ELISA method. Anti-cancer and cytotoxicity studies were carried out by MTT assay. COX-2 seems to be associated with cancers and atypical developments in the duodenal tract. So, a competitive ELISA based COX-2 inhibition assay was done. To validate the inhibitory potentials and to get more insight into the interaction of COX-2 with Cpd1-10, molecular docking was performed. Results: Briefly, the COX-2 inhibitory relative activity was found to be in between the range of 80-92% (Diclofenac showed 84%, IC50 0.95 μM). Conclusion: Cytotoxicity effect of the compounds against breast cancer cell lines found excellent and an extended anticancer study ensured that these compounds are also alternative therapeutic agents against breast cancer. Among all the tested cancer cell lines, the anti- cancer effect on breast cancer was exceptional for the most active compounds Cpd5 and Cpd9.

Subpellicular microtubules associate with an intramembranous particle lattice in the protozoan parasite Toxoplasma gondii

1997 ◽  
Vol 110 (1) ◽  
pp. 35-42 ◽  
Author(s):  
N.S. Morrissette ◽  
J.M. Murray ◽  
D.S. Roos
Keyword(s):  
Toxoplasma Gondii ◽  
Fourier Analysis ◽  
Host Cell ◽  
Morphological Changes ◽  
Shape Change ◽  
Freeze Fracture ◽  
Protozoan Parasite ◽  
Two Dimensional ◽  
Intramembranous Particle ◽  
Analysis Techniques

Application of Fourier analysis techniques to images of isolated, frozen-hydrated subpellicular microtubules from the protozoan parasite Toxoplasma gondii demonstrates a distinctive 32 nm periodicity along the length of the microtubules. A 32 nm longitudinal repeat is also observed in the double rows of intramembranous particles seen in freeze-fracture images of the parasite's pellicle; these rows are thought to overlie the subpellicular microtubules. Remarkably, the 32 nm intramembranous particle periodicity is carried over laterally to the single rows of particles that lie between the microtubule-associated double rows. This creates a two-dimensional particle lattice, with the second dimension at an angle of approximately 75 degrees to the longitudinal rows (depending on position along the length of the parasite). Drugs that disrupt known cytoskeletal components fail to destroy the integrity of the particle lattice. This intramembranous particle organization suggests the existence of multiple cytoskeletal filaments of unknown identity. Filaments associated with the particle lattice provide a possible mechanism for motility and shape change in Toxoplasma: distortion of the lattice may mediate the twirling motility seen upon host-cell lysis, and morphological changes observed during invasion.

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