scholarly journals Insights into Innate Sensing of Prototype Foamy Viruses in Myeloid Cells

Viruses ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1095 ◽  
Author(s):  
Maïwenn Bergez ◽  
Jakob Weber ◽  
Maximilian Riess ◽  
Alexander Erdbeer ◽  
Janna Seifried ◽  
...  
Keyword(s):  
Immune System ◽  
Viral Entry ◽  
Innate Immune System ◽  
Myeloid Cells ◽  
Innate Immune ◽  
Full Length ◽  
Host Cells ◽  
Dependent Manner ◽  
Viral Pathogen ◽  
Foamy Viruses

Foamy viruses (FVs) belong to the Spumaretrovirinae subfamily of retroviruses and are characterized by unique features in their replication strategy. This includes a reverse transcription (RTr) step of the packaged RNA genome late in replication, resulting in the release of particles with a fraction of them already containing an infectious viral DNA (vDNA) genome. Little is known about the immune responses against FVs in their hosts, which control infection and may be responsible for their apparent apathogenic nature. We studied the interaction of FVs with the innate immune system in myeloid cells, and characterized the viral pathogen-associated molecular patterns (PAMPs) and the cellular pattern recognition receptors and sensing pathways involved. Upon cytoplasmic access, full-length but not minimal vector genome containing FVs with active reverse transcriptase, induced an efficient innate immune response in various myeloid cells. It was dependent on cellular cGAS and STING and largely unaffected by RTr inhibition during viral entry. This suggests that RTr products, which are generated during FV morphogenesis in infected cells, and are therefore already present in FV particles taken up by immune cells, are the main PAMPs of FVs with full-length genomes sensed in a cGAS and STING-dependent manner by the innate immune system in host cells of the myeloid lineage.

scholarly journals Differential Activation of Innate Immune Responses by Adenovirus and Adeno-Associated Virus Vectors

2002 ◽  
Vol 76 (9) ◽  
pp. 4580-4590 ◽  
Author(s):  
Anne-Kathrin Zaiss ◽  
Qiang Liu ◽  
Gloria P. Bowen ◽  
Norman C. W. Wong ◽  
Jeffrey S. Bartlett ◽  
...  
Keyword(s):  
Immune System ◽  
Intravenous Administration ◽  
Innate Immune System ◽  
Innate Immune ◽  
Target Cells ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Adeno Associated Virus ◽  
Tnf Α ◽  
Adenovirus Vectors

ABSTRACT Adenovirus vectors induce acute inflammation of infected tissues due to activation of the innate immune system and expression of numerous chemokines and cytokines in transduced target cells. In contrast, adeno-associated virus (AAV) vectors are not associated with significant inflammation experimentally or clinically. We tested the ability of AAV vectors to induce the expression of chemokines in vitro and to activate the innate immune system in vivo. In human HeLa cells and murine renal epithelium-derived cells (REC cells) the adenovirus vector AdlacZ induced the expression of multiple inflammatory chemokines including RANTES, interferon-inducible protein 10 (IP-10), interleukin-8 (IL-8), MIP-1β, and MIP-2 in a dose-dependent manner. The use of AAVlacZ did not induce the expression of these chemokines above baseline levels despite 40-fold-greater titers than AdlacZ and greater amounts of intracellular AAVlacZ genomes according to Southern and slot blot analysis. This finding confirmed that the lack of AAVlacZ induction of chemokine was not due to reduced transduction. In DBA/2 mice, the intravenous administration of 2.5 × 1011 particles of AAVlacZ resulted in the rapid induction of liver tumor necrosis factor alpha (TNF-α), RANTES, IP-10, MIP-1β, MCP-1, and MIP-2 mRNAs. However, 6 h following injection, chemokine mRNA levels returned to baseline. As expected, administration of 10-fold less AdlacZ caused an induction of liver TNF-α and chemokine mRNAs that persisted for more than 24 h posttransduction. Whereas intravenous administration of 2.5 × 1011 particles of AAVlacZ triggered a transient infiltration of neutrophils and CD11b+ cells into liver, this response stood in contrast to widespread inflammation and toxicity induced by AdlacZ. Kupffer cell depletion abolished AAVlacZ but not AdlacZ-induced chemokine expression and neutrophil infiltration. In summary, these results show that AAV vectors activate the innate immune system to a lesser extent than do adenovirus vectors and offer a possible explanation for the reduced inflammatory properties of AAV compared to adenovirus vectors.

scholarly journals Granulocyte CEACAM3 Is a Phagocytic Receptor of the Innate Immune System that Mediates Recognition and Elimination of Human-specific Pathogens

2004 ◽  
Vol 199 (1) ◽  
pp. 35-46 ◽  
Author(s):  
Tim Schmitter ◽  
Franziska Agerer ◽  
Lisa Peterson ◽  
Petra Münzner ◽  
Christof R. Hauck
Keyword(s):  
Immune System ◽  
Tyrosine Kinases ◽  
Innate Immune System ◽  
Small Gtpase ◽  
Innate Immune ◽  
Dominant Negative ◽  
Host Cells ◽  
Human Pathogens ◽  
Human Granulocytes ◽  
Human Specific

Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) are used by several human pathogens to anchor themselves to or invade host cells. Interestingly, human granulocytes express a specific isoform, CEACAM3, that participates together with CEACAM1 and CEACAM6 in the recognition of CEACAM-binding microorganisms. Here we show that CEACAM3 can direct efficient, opsonin-independent phagocytosis of CEACAM-binding Neisseria, Moraxella, and Haemophilus species. CEACAM3- but not CEACAM6-mediated uptake is blocked by dominant-negative versions of the small GTPase Rac. Moreover, CEACAM3 engagement triggers membrane recruitment and increased GTP loading of Rac that are not observed upon bacterial binding to CEACAM6. Internalization and Rac stimulation are also inhibited by compromising the integrity of an immunoreceptor tyrosine-based activation motif (ITAM)–like sequence in the cytoplasmic tail of CEACAM3 or by interference with Src family protein tyrosine kinases that phosphorylate CEACAM3. In contrast to interfering with CEACAM6, blockage of CEACAM3-mediated events reduces the ability of primary human granulocytes to internalize and eliminate CEACAM-binding bacteria, indicating an important role of CEACAM3 in the control of human-specific pathogens by the innate immune system.

scholarly journals Adenoviruses Use Lactoferrin as a Bridge for CAR-Independent Binding to and Infection of Epithelial Cells

2006 ◽  
Vol 81 (2) ◽  
pp. 954-963 ◽  
Author(s):  
Cecilia Johansson ◽  
Mari Jonsson ◽  
Marko Marttila ◽  
David Persson ◽  
Xiao-Long Fan ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Innate Immune System ◽  
Innate Immune ◽  
Host Cells ◽  
Tear Fluid ◽  
Adenovirus Infection ◽  
Dependent Manner ◽  
Polarized Cells ◽  
Adenovirus Receptor ◽  
Dose Dependent

ABSTRACT Most adenoviruses bind to the coxsackie- and adenovirus receptor (CAR). Surprisingly, CAR is not expressed apically on polarized cells and is thus not easily available to viruses. Consequently, alternative mechanisms for entry of coxsackievirus and adenovirus into cells have been suggested. We have found that tear fluid promotes adenovirus infection, and we have identified human lactoferrin (HLf) as the tear fluid component responsible for this effect. HLf alone was found to promote binding of adenovirus to epithelial cells in a dose-dependent manner and also infection of epithelial cells by adenovirus. HLf was also found to promote gene delivery from an adenovirus-based vector. The mechanism takes place at the binding stage and functions independently of CAR. Thus, we have identified a novel binding mechanism whereby adenovirus hijacks HLf, a component of the innate immune system, and uses it as a bridge for attachment to host cells.

Effect of plinabulin, a novel late-clinical stage immunotherapeutic agent on the adaptive and innate immune system.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 8-8
Author(s):  
Ramon W. Mohanlal ◽  
Lan Huang
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Clinical Stage ◽  
Onset Time ◽  
Immune Defense ◽  
Innate Immune ◽  
Dependent Manner ◽  
Breast Cancer Patients ◽  
Post Dose ◽  
The Impact

8 Background: Plinabulin (Plin) is a small molecule Dendritic Cell modulator, which in the presence of antigen, increases T-cell proliferation in an antigen-dependent manner marrow. The addition of Plin to Docetaxel (Doc) improved mOS with 4.6 months vs Docetaxel monotherapy, and prolonged DoR with more than 1 year (p < 0.05), which is indicative of an immune-mediated mechanism of action (Mohanlal, ASCO-SITC 2017). Neutrophils are our first line of innate immune defense against foreign invaders. We previously reported that Plinabulin prevents chemotherapy (Chemo) Induced Neutropenia (CIN) in patients receiving Doc or TAC throughout the cycle (Doc, Doxorubicin, Cyclophosphamide) (Blayney ASH 2018, St Gallen 2019). Here we analyzed the onset time of neutrophil increase following Plin administration. In addition, we analyzed the impact of Plin on plasma haptoglobin, which is an acute phase protein with anti-inflammatory effects together with immune-enhancing effects and is an integral part of innate immunity (Kristiansen Nature 2001). Methods: Absolute neutrophil count (ANC) and haptoglobin data were analyzed from Phase 2 study BPI-2358-106 (NCT03294577) with 10 (n = 15), 20 (n = 15) and 30 mg/m2 (n = 12) Plin in Breast Cancer patients receiving TAC. Plin was administered on Day 1. ANC and Haptoglobin were analyzed by a Central Laboratory (Covance), from blood draws at predose, and post-dose Plin at Day 2,3,6,7,8,9,10,11,12,13 and 15, and changes relative to predose value were evaluated. Results: Plin dose-dependently increased ANC within 1 day (P < 0.001) and Haptoglobin within 3 days (P < 0.03) of dosing. Mean haptoglobin (P < 0.0005) and ANC (P < 0.001) levels increased with ~two-fold vs baseline levels. ANC levels remained increased for approximately 1 week and haptoglobin levels for > 3 weeks. Conclusions: Based on Plinabulin’s ability to stimulate the innate system, together with its previously reported evidence as a potent activator of the adaptive immune system (Mohanlal, ASCO-SITC 2017), it is concluded that Plinabulin is a potent stimulator of the adaptive and innate immune system. Clinical trial information: NCT03294577.

scholarly journals Effects of Overexpression of the Egyptian Fruit Bat Innate Immune Genes on Filovirus Infections in the Host Cells

2021 ◽  
Vol 1 ◽  
Author(s):  
Ivan V. Kuzmin ◽  
Palaniappan Ramanathan ◽  
Christopher F. Basler ◽  
Alexander Bukreyev
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Innate Immune ◽  
Host Cells ◽  
Type I ◽  
Fluorescent Reporter ◽  
Immune Genes ◽  
Fruit Bat ◽  
Virus Clearance ◽  
Innate Immune Genes

Bats constitute a large and diverse group of mammals with unique characteristics. One of these is the ability of bats to maintain various pathogens, particularly viruses, without evidence of disease. The innate immune system has been implicated as one of the important components involved in this process. However, in contrast to the human innate immune system, little data is available for bats. In the present study we generated 23 fusion constructs of innate immune genes of Egyptian fruit bat (Rousettus aegyptiacus) with mCherry as a fluorescent reporter. We evaluated the effects of overexpressing these genes on the replication of Marburg and Ebola viruses in the Egyptian fruit bat cell line R06EJ. Both viruses were substantially inhibited by overexpression of type I, II and III interferons, as well as by DDX58 (RIG-I), IFIH1, and IRF1. Our observations suggest that the broad antiviral activity of these genes reported previously in human cells is conserved in Egyptian fruit bats and these possess anti-filovirus activities that may contribute to the efficient virus clearance.

Severe respiratory syncytial virus disease in preterm infants: a case of innate immaturity

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-216291
Author(s):  
Jeremy Anderson ◽  
Lien Anh Ha Do ◽  
Danielle Wurzel ◽  
Zheng Quan Toh ◽  
Kim Mulholland ◽  
...  
Keyword(s):  
Immune System ◽  
Respiratory Syncytial Virus ◽  
Preterm Infants ◽  
Innate Immune System ◽  
Virus Disease ◽  
Innate Immune ◽  
Term Infants ◽  
Viral Pathogen ◽  
Immune Biomarkers ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) is the most common viral pathogen associated with acute lower respiratory tract infection (LRTI) in children under 5 years of age. Severe RSV disease is associated with the development of chronic respiratory complications such as recurrent wheezing and asthma. A common risk factor for developing severe RSV disease is premature gestation and this is largely due to an immature innate immune system. This increases susceptibility to RSV since the innate immune system is less able to protect against pathogens at a time when adaptive immunity has not fully developed. This review focuses on comparing different aspects of innate immunity between preterm and term infants to better understand why preterm infants are more susceptible to severe RSV disease. Identifying early life innate immune biomarkers associated with the development of severe RSV disease, and understanding how these compare between preterm and term infants, remains a critically important question that would aid the development of interventions to reduce the burden of disease in this vulnerable population.

scholarly journals LA RESPUESTA INMUNITARIA FRENTE AL VIRUS SARS-CoV-2

2020 ◽  
Vol 3 (9) ◽  
pp. 64-86
Author(s):  
SERGIO ROBERTO AGUILAR-RUIZ ◽  
FRANCISCO JAVIER SÁNCHEZ-PEÑA
Keyword(s):  
Immune System ◽  
Viral Entry ◽  
Immune Cells ◽  
Innate Immune System ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Adaptive Immune ◽  
Infected Cells ◽  
Systemic Pathology

The immune response against SARS-CoV-2 is similar to that against other viruses, where the innate immune system acts at early stages through the secretion of type 1 interferon (type 1 IFN), which prevents viral replication and the activation of natural killer (NK) cells. Later, the adaptive immune system acts through CD8+ cytotoxic T-lymphocytes and antibody production, which aim to destroy infected cells and block viral entry into cells. All the above leads to the elimination of the virus and mild symptomatology. However, in individuals with a weakened immune system, the viral infection spreads and leads to a potent inflammatory response, which leads to the recruitment of immune cells to the lungs, where they can cause severe pulmonary and even systemic pathology.

Respiratory Burst Factors in Nigerian Patients with COVID-19

2021 ◽  
Vol 7 (1) ◽  
pp. 24-28
Author(s):  
Ganiyu Arinola ◽  
Fabian Edem ◽  
Temitope Alonge
Keyword(s):  
Immune System ◽  
Respiratory Burst ◽  
Innate Immune System ◽  
Age Groups ◽  
Innate Immune ◽  
Host Cells ◽  
Sod Activity ◽  
Female Patients ◽  
H2o2 Level ◽  
Control Plasma

Respiratory burst function resulting in the release of reactive oxygen species from leucocytes is one of the key mechanisms of innate immune system to prevent the establishment of intracellular pathogens in the host cells. Previous studies on COVID-19 patients concentrated on adaptive immunity while study on respiratory burst functions is lacking. Respiratory burst mediators levels [nitric oxide (NO) and hydrogen peroxide (H2O2)] and respiratory burst enzymes activities [Catalase (CAT), Myeloperoxidase (MPO) and Superoxide dismutase (SOD)] were quantitated in the plasma Mean plasma NO level, MPO activity and H2O2 level were significantly decreased while SOD activity was significantly increased in COVID-19 patients at admission compared with control. Mean plasma NO level significantly decreased while MPO activity was significantly increased in COVID-19 patients at discharge compared with control. Plasma NO level, H2O2 level and MPO activity were significantly increased in COVID-19 patients at discharge compared with COVID-19 patients at admission. In COVID-19 patients that spent ?10days in admission, the levels of NO and H2O2 were significantly increased compared with the levels of NO and H2O2 in COVID-19 patients that spent <10days in admission. In male COVID-19 patients, NO level and MPO activity were significantly increased compared with MPO activity in female patients. In COVID-19 patients ?40years of age, NO level was significantly decreased while MPO activity was significantly increased compared with COVID-19 patients <40yrs of age. In male COVID-19 patients, NO level and MPO activity was significantly increased compared with MPO activity in female patients. It could be concluded from this study that factors of respiratory burst which are components of the innate immune system are altered in COVID-19 patients and could be involved in the immune-pathogenecity of SARS-CoV-2; and that MPO coupled with NO may explain differential severities of COVID-19 among genders and age groups.

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