scholarly journals The in vitro host cell immune response to bovine-adapted Staphylococcus aureus varies according to bacterial lineage

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mark P. Murphy ◽  
Dagmara A. Niedziela ◽  
Finola C. Leonard ◽  
Orla M. Keane
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Response ◽  
Host Cell ◽  
Cell Immune Response ◽  
Bacterial Lineage

Tofacitinib modulates the VZV-specific CD4+ T cell immune response in vitro in lymphocytes of patients with rheumatoid arthritis

Rheumatology ◽  
2019 ◽  
Vol 58 (11) ◽  
pp. 2051-2060 ◽  
Author(s):  
Giovanni Almanzar ◽  
Felix Kienle ◽  
Marc Schmalzing ◽  
Anna Maas ◽  
Hans-Peter Tony ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Granzyme B ◽  
Janus Kinase ◽  
Cell Immune Response ◽  
Dependent Manner ◽  
Th1 Response

AbstractObjectiveRA is a chronic inflammatory disease characterized by lymphocyte infiltration and release of inflammatory cytokines. Previous studies have shown that treatment with Janus kinase inhibitors, such as tofacitinib, increased the incidence rate of herpes zoster compared with conventional DMARDs. Therefore, this study aimed to investigate the effect of tofacitinib on the varicella-zoster-virus (VZV)-specific T cell immune response.MethodsThe effect of tofacitinib on the VZV-specific T cell immune response was determined by evaluating the IFNγ production, the proliferative capacity, the VZV-induced differentiation into effector and memory T cells, the expression of activation marker CD69 and helper T cell type 1 (Th1)-characteristic chemokine receptors, such as CXCR3 and CCR5, as well as cytotoxic activity (perforin and granzyme B expression) of CD4+ T cells of patients with RA compared with healthy donors upon stimulation with VZV antigen in vitro.ResultsTofacitinib significantly reduced the IFNγ production, proliferation, activation, and CXCR3 expression of VZV-specific CD4+ T cells in a dose-dependent manner in short- and long-term lymphocyte culture. No effect on the distribution of naive, effectors or memory, or on the expression of perforin or granzyme B by VZV-specific CD4+ T cells was observed.ConclusionThis study showed that tofacitinib significantly modulated the Th1 response to VZV. The poor VZV-specific cellular immune response in patients with RA may be considered in recommendations regarding appropriate vaccination strategies for enhancing the VZV-specific Th1 response.

scholarly journals Internalization of Staphylococcus aureus by Human Corneal Epithelial Cells: Role of Bacterial Fibronectin-Binding Protein and Host Cell Factors

2002 ◽  
Vol 70 (8) ◽  
pp. 4697-4700 ◽  
Author(s):  
Bradley D. Jett ◽  
Michael S. Gilmore
Keyword(s):  
Staphylococcus Aureus ◽  
Epithelial Cells ◽  
Host Cell ◽  
Corneal Epithelial Cells ◽  
Corneal Epithelial ◽  
Viable Bacteria ◽  
Host Cell Factors ◽  
Human Corneal Epithelial Cells ◽  
Fibronectin Binding

ABSTRACT Wild-type Staphylococcus aureus was observed to be capable of invading human corneal epithelial cells (HCEC) in vitro. Internalization of S. aureus required expression of fibronectin-binding proteins (FnBPs); the capacity of an FnBP-deficient isogenic strain to invade HCEC was reduced by more than 99%. The binding of S. aureus to HCEC did not require viable bacteria, since UV-killed cells were observed to adhere efficiently. Invasion of HCEC by S. aureus involved active host cell mechanisms; uptake was nearly completely eliminated by cytochalasin D and genistein. These data suggest that FnBPs play a key role in host-parasite interactions and may serve as an important adhesin or invasin in ulcerative keratitis caused by S. aureus.

Biosurfactants of Lactobacillus helveticus for biodiversity inhibit the biofilm formation of Staphylococcus aureus and cell invasion

2019 ◽  
Vol 14 (13) ◽  
pp. 1133-1146 ◽  
Author(s):  
Xinpeng Jiang ◽  
Xin Yan ◽  
Shanshan Gu ◽  
Yan Yang ◽  
Lili Zhao ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Host Cell ◽  
Biofilm Formation ◽  
Lactobacillus Helveticus ◽  
Real Time Quantitative Pcr ◽  
Autoinducer 2 ◽  
New Strategy ◽  
Better Than

Aim: This study aimed to evaluate the differences of biosurfactants produced by two Lactobacillus helveticus strains against the biofilm formation of Staphylococcus aureus in vitro and in vivo. Materials & methods: Scanning electron microscopy, Real time-quantitative PCR (RT-qPCR) and cell assay were used to analyze the inhibiting effect of biosurfactants against biofilm formation. Results & conclusion: Results showed that the biosurfactants have anti-adhesive and inhibiting effects on biofilm formation in vivo and in vitro. The biofilm-formative genes and autoinducer-2 signaling regulated these characteristics, and the biosurfactant L. helveticus 27170 is better than that of 27058. Host cell adhesion and invasion results indicated that the biosurfactants L. helveticus prevented the S. aureus invading the host cell, which may be a new strategy to eliminate biofilms.

scholarly journals Structure-based discovery of a small-molecule inhibitor of methicillin-resistant Staphylococcus aureus virulence

2020 ◽  
Vol 295 (18) ◽  
pp. 5944-5959 ◽  
Author(s):  
Jie Liu ◽  
Lina Kozhaya ◽  
Victor J. Torres ◽  
Derya Unutmaz ◽  
Min Lu
Keyword(s):  
Staphylococcus Aureus ◽  
Host Cell ◽  
Cell Attachment ◽  
Host Cell Membrane ◽  
Methicillin Resistant ◽  
Molecule Inhibitor ◽  
Membrane Perforation ◽  
Host Cell Attachment ◽  
Mrsa Strains

The rapid emergence and dissemination of methicillin-resistant Staphylococcus aureus (MRSA) strains poses a major threat to public health. MRSA possesses an arsenal of secreted host-damaging virulence factors that mediate pathogenicity and blunt immune defenses. Panton–Valentine leukocidin (PVL) and α-toxin are exotoxins that create lytic pores in the host cell membrane. They are recognized as being important for the development of invasive MRSA infections and are thus potential targets for antivirulence therapies. Here, we report the high-resolution X-ray crystal structures of both PVL and α-toxin in their soluble, monomeric, and oligomeric membrane-inserted pore states in complex with n-tetradecylphosphocholine (C14PC). The structures revealed two evolutionarily conserved phosphatidylcholine-binding mechanisms and their roles in modulating host cell attachment, oligomer assembly, and membrane perforation. Moreover, we demonstrate that the soluble C14PC compound protects primary human immune cells in vitro against cytolysis by PVL and α-toxin and hence may serve as the basis for the development of an antivirulence agent for managing MRSA infections.

scholarly journals Deubiquitinating Enzymes in Coronaviruses and Possible Therapeutic Opportunities for COVID-19

2020 ◽  
Vol 21 (10) ◽  
pp. 3492 ◽  
Author(s):  
Valentino Clemente ◽  
Padraig D’Arcy ◽  
Martina Bazzaro
Keyword(s):  
Immune Response ◽  
Cysteine Proteases ◽  
Cell Immune Response ◽  
Deubiquitinating Enzymes ◽  
Improve Patient Survival ◽  
Replicase Proteins ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Improve Patient

Following the outbreak of novel severe acute respiratory syndrome (SARS)-coronavirus (CoV)2, the majority of nations are struggling with countermeasures to fight infection, prevent spread and improve patient survival. Considering that the pandemic is a recent event, no large clinical trials have been possible and since coronavirus specific drug are not yet available, there is no strong consensus on how to treat the coronavirus disease 2019 (COVID-19) associated viral pneumonia. Coronaviruses code for an important multifunctional enzyme named papain-like protease (PLP), that has many roles in pathogenesis. First, PLP is one of the two viral cysteine proteases, along with 3-chymotripsin-like protease, that is responsible for the production of the replicase proteins required for viral replication. Second, its intrinsic deubiquitinating and deISGylating activities serve to antagonize the host’s immune response that would otherwise hinder infection. Both deubiquitinating and deISGylating functions involve the removal of the small regulatory polypeptides, ubiquitin and ISG15, respectively, from target proteins. Ubiquitin modifications can regulate the innate immune response by affecting regulatory proteins, either by altering their stability via the ubiquitin proteasome pathway or by directly regulating their activity. ISG15 is a ubiquitin-like modifier with pleiotropic effects, typically expressed during the host cell immune response. PLP inhibitors have been evaluated during past coronavirus epidemics, and have showed promising results as an antiviral therapy in vitro. In this review, we recapitulate the roles of PLPs in coronavirus infections, report a list of PLP inhibitors and suggest possible therapeutic strategies for COVID-19 treatment, using both clinical and preclinical drugs.

scholarly journals Identification of Staphylococcus aureus Proteins Recognized by the Antibody-Mediated Immune Response to a Biofilm Infection

2006 ◽  
Vol 74 (6) ◽  
pp. 3415-3426 ◽  
Author(s):  
Rebecca A. Brady ◽  
Jeff G. Leid ◽  
Anne K. Camper ◽  
J. William Costerton ◽  
Mark E. Shirtliff
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Response ◽  
Immune System ◽  
Two Dimensional Gel Electrophoresis ◽  
A Cell ◽  
Microarray Analyses ◽  
Gene Expression Levels ◽  
Biofilm Infection

ABSTRACT Staphylococcus aureus causes persistent, recurrent infections (e.g., osteomyelitis) by forming biofilms. To survey the antibody-mediated immune response and identify those proteins that are immunogenic in an S. aureus biofilm infection, the tibias of rabbits were infected with methicillin-resistant S. aureus to produce chronic osteomyelitis. Sera were collected prior to infection and at 14, 28, and 42 days postinfection. The sera were used to perform Western blot assays on total protein from biofilm grown in vitro and separated by two-dimensional gel electrophoresis. Those proteins recognized by host antibodies in the harvested sera were identified via matrix-assisted laser desorption ionization-time of flight analysis. Using protein from mechanically disrupted total and fractionated biofilm protein samples, we identified 26 and 22 immunogens, respectively. These included a cell surface-associated β-lactamase, lipoprotein, lipase, autolysin, and an ABC transporter lipoprotein. Studies were also performed using microarray analyses and confirmed the biofilm-specific up-regulation of most of these genes. Therefore, although the biofilm antigens are recognized by the immune system, the biofilm infection can persist. However, these proteins, when delivered as vaccines, may be important in directing the immune system toward an early and effective antibody-mediated response to prevent chronic S. aureus infections. Previous works have identified S. aureus proteins that are immunogenic during acute infections, such as sepsis. However, this is the first work to identify these immunogens during chronic S. aureus biofilm infections and to simultaneously show the global relationship between the antigens expressed during an in vivo infection and the corresponding in vitro transcriptomic and proteomic gene expression levels.

scholarly journals Development of a Conserved Chimeric Vaccine for Induction of Strong Immune Response against Staphylococcus aureus Using Immunoinformatics Approaches

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1038
Author(s):  
Rahul Chatterjee ◽  
Panchanan Sahoo ◽  
Soumya Ranjan Mahapatra ◽  
Jyotirmayee Dey ◽  
Mrinmoy Ghosh ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Response ◽  
Multidrug Resistant ◽  
Host Cells ◽  
Dynamics Simulation ◽  
Population Coverage ◽  
Strong Immune Response ◽  
Chimeric Vaccine

Staphylococcus aureus is one of the most notorious Gram-positive bacteria with a very high mortality rate. The WHO has listed S. aureus as one of the ESKAPE pathogens requiring urgent research and development efforts to fight against it. Yet there is a major layback in the advancement of effective vaccines against this multidrug-resistant pathogen. SdrD and SdrE proteins are attractive immunogen candidates as they are conserved among all the strains and contribute specifically to bacterial adherence to the host cells. Furthermore, these proteins are predicted to be highly antigenic and essential for pathogen survival. Therefore, in this study, using the immunoinformatics approach, a novel vaccine candidate was constructed using highly immunogenic conserved T-cell and B-cell epitopes along with specific linkers, adjuvants, and consequently modeled for docking with human Toll-like receptor 2. Additionally, physicochemical properties, secondary structure, disulphide engineering, and population coverage analysis were also analyzed for the vaccine. The constructed vaccine showed good results of worldwide population coverage and a promising immune response. For evaluation of the stability of the vaccine-TLR-2 docked complex, a molecular dynamics simulation was performed. The constructed vaccine was subjected to in silico immune simulations by C-ImmSim and Immune simulation significantly provided high levels of immunoglobulins, T-helper cells, T-cytotoxic cells, and INF-γ. Lastly, upon cloning, the vaccine protein was reverse transcribed into a DNA sequence and cloned into a pET28a (+) vector to ensure translational potency and microbial expression. The overall results of the study showed that the designed novel chimeric vaccine can simultaneously elicit humoral and cell-mediated immune responses and is a reliable construct for subsequent in vivo and in vitro studies against the pathogen.

scholarly journals Regulation of memory B-cell survival by the BH3-only protein Puma

Blood ◽  
2011 ◽  
Vol 118 (15) ◽  
pp. 4120-4128 ◽  
Author(s):  
Cyril Clybouw ◽  
Silke Fischer ◽  
Marie Thérèse Auffredou ◽  
Patricia Hugues ◽  
Catherine Alexia ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
B Cell ◽  
Cell Survival ◽  
Family Member ◽  
Cell Immune Response ◽  
Memory B Cell ◽  
B Cell Survival

Abstract Apoptosis is crucial for immune system homeostasis, including selection and survival of long-lived antibody-forming cells and memory cells. The interactions between proapoptotic and pro-survival proteins of the Bcl-2 family are critical for this process. In this report, we show that expression of the proapoptotic BH3-only Bcl-2 family member Puma was selectively up-regulated on in vitro activation with antigens or mitogens of both human and mouse B cells. Puma expression coincided in vivo, with the prosurvival Bcl-2 family member Mcl-1 within the germinal centers and its expression correlates with the germinal center like phenotype of Burkitt lymphoma. Experiments performed in Puma-deficient mice revealed that Puma is essential for apoptosis of mitogen-activated B cells in vitro and for the control of memory B-cell survival. In conclusion, using both human and murine models, our data show that Puma has a major role in the T cell– dependent B-cell immune response. These data demonstrate that Puma is a major regulator of memory B lymphocyte survival and therefore a key molecule in the control of the immune response.

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