scholarly journals Stimulation of immunity-linked genes by membrane disruption is linked to Golgi function and the ARF-1 GTPase

2021 ◽  
Author(s):  
Christofer M Welsh ◽  
Lorissa J Smulan ◽  
Matthew J Fanelli ◽  
Dominuque S Lui ◽  
Amy Karol Walker
Keyword(s):  
Immune Response ◽  
Stress Response ◽  
Protein Secretion ◽  
Secretory Pathway ◽  
Metabolic Changes ◽  
Membrane Disruption ◽  
Intrinsic Cues ◽  
Lipid Imbalance ◽  
Adp Ribosylation Factor ◽  
Stimulation Of

Immune-linked genes (ILGs) are activated in response to pathogens but can also be activated by lipid imbalance. Why pathogen attack and metabolic changes both impact ILG activation is unclear. Organelles in the secretory pathway have distinct protein and lipid components and genetically separable stress programs. These stress pathways activate restorative transcriptional programs when lipid ratios become unbalanced or during dysregulated protein folding and trafficking. We find that ILGs are specifically activated when membrane phosphatidylcholine ratios change in the secretory pathway. Consistent with this result, disruption of Golgi function in mutations targeting the ADP-ribosylation factor ARF-1 also activates ILG expression. Since increased protein secretion is altered by metabolic changes and pathogen responses, our data argue that ILG upregulation is a conserved, coordinated response to changes in trafficking resulting from intrinsic cues (lipid changes) or extrinsic stimulation (during the immune response). These findings uncover important and previously unexplored links between metabolism and the stress response.

Membrane traffic related to endosome dynamics and protein secretion in filamentous fungi

2021 ◽  
Author(s):  
Yujiro Higuchi
Keyword(s):  
Filamentous Fungi ◽  
Protein Secretion ◽  
Secretory Pathway ◽  
Molecular Mechanisms ◽  
Membrane Traffic ◽  
Early Endosome ◽  
Protein Glycosylation ◽  
Hyphal Cell ◽  
Cell Factories ◽  
Membrane Contacts

ABSTRACT In eukaryotic cells, membrane-surrounded organelles are orchestrally organized spatiotemporally under environmental situations. Among such organelles, vesicular transports and membrane contacts occur to communicate each other, so-called membrane traffic. Filamentous fungal cells are highly polarized and thus membrane traffic is developed to have versatile functions. Early endosome (EE) is an endocytic organelle that dynamically exhibits constant long-range motility through the hyphal cell, which is proven to have physiological roles, such as other organelle distribution and signal transduction. Since filamentous fungal cells are also considered as cell factories, to produce valuable proteins extracellularly, molecular mechanisms of secretory pathway including protein glycosylation have been well investigated. In this review, molecular and physiological aspects of membrane traffic especially related to EE dynamics and protein secretion in filamentous fungi are summarized, and perspectives for application are also described.

Stimulation of immune response by polymannuronic-guluronic acid in mice

1971 ◽  
Vol 27 (8) ◽  
pp. 953-954 ◽  
Author(s):  
T. Diamantstein ◽  
G. Odenwald ◽  
D. Odenwald
Keyword(s):  
Immune Response ◽  
Guluronic Acid ◽  
Stimulation Of

scholarly journals Modulation of Antigen Display on PapMV Nanoparticles Influences Its Immunogenicity

Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 33
Author(s):  
Marie-Eve Laliberté-Gagné ◽  
Marilène Bolduc ◽  
Caroline Garneau ◽  
Santa-Mariela Olivera-Ugarte ◽  
Pierre Savard ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza A ◽  
Matrix Protein ◽  
Cell Epitope ◽  
Vaccine Antigen ◽  
Vaccine Platform ◽  
Peptide Antigens ◽  
C Terminus ◽  
The Impact ◽  
Stimulation Of

Background: The papaya mosaic virus (PapMV) vaccine platform is a rod-shaped nanoparticle made of the recombinant PapMV coat protein (CP) self-assembled around a noncoding single-stranded RNA (ssRNA) template. The PapMV nanoparticle induces innate immunity through stimulation of the Toll-like receptors (TLR) 7 and 8. The display of the vaccine antigen at the surface of the nanoparticle, associated with the co-stimulation signal via TLR7/8, ensures a strong stimulation of the immune response, which is ideal for the development of candidate vaccines. In this study, we assess the impact of where the peptide antigen is fused, whether at the surface or at the extremities of the nanoparticles, on the immune response directed to that antigen. Methods: Two different peptides from influenza A virus were used as model antigens. The conserved M2e peptide, derived from the matrix protein 2 was chosen as the B-cell epitope, and a peptide derived from the nucleocapsid was chosen as the cytotoxic T lymphocytes (CTL) epitope. These peptides were coupled at two different positions on the PapMV CP, the N- (PapMV-N) or the C-terminus (PapMV-C), using the transpeptidase activity of Sortase A (SrtA). The immune responses, both humoral and CD8+ T-cell-mediated, directed to the peptide antigens in the two different fusion contexts were analyzed and compared. The impact of coupling density at the surface of the nanoparticle was also investigated. Conclusions: The results demonstrate that coupling of the peptide antigens at the N-terminus (PapMV-N) of the PapMV CP led to an enhanced immune response to the coupled peptide antigens as compared to coupling to the C-terminus. The difference between the two vaccine platforms is linked to the enhanced capacity of the PapMV-N vaccine platform to stimulate TLR7/8. We also demonstrated that the strength of the immune response increases with the density of coupling at the surface of the nanoparticles.

Investigation of the role of microtubules in protein secretion from lactating mouse mammary epithelial cells

1992 ◽  
Vol 102 (2) ◽  
pp. 239-247 ◽  
Author(s):  
M.E. Rennison ◽  
S.E. Handel ◽  
C.J. Wilde ◽  
R.D. Burgoyne
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cells ◽  
Protein Secretion ◽  
Secretory Pathway ◽  
Mammary Epithelial Cells ◽  
Early Stage ◽  
Major Effect ◽  
Vesicle Transport ◽  
Mammary Epithelial ◽  
Mammary Cells

Disruption of microtubules has been shown to reduce protein secretion from lactating mammary epithelial cells. To investigate the involvement of microtubules in the secretory pathway in these cells we have examined the effect of nocodazole on protein secretion from mammary epithelial cells derived from the lactating mouse. Mouse mammary cells have extensive microtubule networks and 85% of their tubulin was in a polymeric form. Treatment with 1 micrograms/ml nocodazole converted most of the tubulin into a soluble form. In a continuous labelling protocol it was found that nocodazole did not interfere with protein synthesis but over a 5 h period secretion was markedly inhibited. To determine whether the inhibition was at the level of early or late stages of the secretory pathway mammary cells were pulse-labelled for 1 h to label protein throughout the secretory pathway before nocodazole treatment. When secretion was subsequently assayed it was found to be slower and only partially inhibited. These findings suggest that the major effect of nocodazole is on an early stage of the secretory pathway and that microtubules normally facilitate vesicle transport to the plasma membrane. An involvement of microtubules in vesicle transport to the plasma membrane is consistent with an observed accumulation of casein vesicles in nocodazole-treated cells. Exocytosis stimulated by the calcium ionophore ionomycin was unaffected by nocodazole treatment. We conclude from these results that the major effect of nocodazole is at an early stage of the secretory pathway, one possible target being casein vesicle biogenesis in the trans-Golgi network.

Vitamin D regulates the expression of immune and stress response genes in dengue virus-infected macrophages by inducing specific microRNAs

MicroRNA ◽  
2021 ◽  
Vol 11 ◽  
Author(s):  
Geysson Javier Fernandez ◽  
Jorge Andrés Castillo ◽  
Diana Marcela Giraldo ◽  
Silvio Urcuqui-Inchima
Keyword(s):  
Vitamin D ◽  
Immune Response ◽  
Stress Response ◽  
Dengue Virus ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Denv Infection ◽  
High Dose ◽  
Regulatory Pathways ◽  
Stress Response Genes

Background: The pathogenesis associated with Dengue virus (DENV) infection is marked by the impairment of host immune response. Consequently, the modulation of immune response has emerged as an important therapeutic target for the control of DENV infection. Vitamin D has been shown to regulate the immune response in DENV infection, although the molecular mechanism remains poorly understood. Post-transcriptional regulation of mRNA by miRNAs offers an opportunity to gain insight into the immunomodulation mediated by vitamin D Objective: Previously, it has been observed that a high dose of vitamin D (4000 IU) decreased DENV-2 infection and inflammatory response in monocyte-derived macrophages (MDMs). Here, we examine whether high or low doses of vitamin D supplements exert differential effect on miRNA expression in DENV-infected macrophages Methods: We analyzed miRNA expression profiles in MDMs isolated from healthy individuals who were given either 1000 or 4000 IU/day of vitamin D for 10 days. MDMs before or after vitamin D supplementation were challenged with DENV-2, and miRNAs profiles were analyzed by qPCR arrays. Results: DENV-2 infected MDMs supplemented with 4000 IU, showed up-regulation of miR-374a-5p, miR-363-3p, miR-101-3p, miR-9-5p, miR-34a-5p, miR-200a-3p, and the family of miRNAs miR-21-5p, and miR-590-p. The miRNA profile and predicted target mRNAs suggested regulatory pathways in MDMs obtained from healthy donors who received higher doses of vitamin D. These DENV-2 infected MDMs expressed a unique set of miRNAs that target immune and cellular stress response genes. Conclusion: The results suggest vitamin D dose-dependent differential expression of miRNAs target key signaling pathways of the pathogenesis of dengue disease.

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