scholarly journals The innate immune system and neurogenesis as modulating mechanisms of electroconvulsive therapy in pre-clinical studies

2020 ◽  
Vol 34 (10) ◽  
pp. 1086-1097
Author(s):  
Juliette Giacobbe ◽  
Carmine M Pariante ◽  
Alessandra Borsini
Keyword(s):  
Cell Proliferation ◽  
Immune System ◽  
Electroconvulsive Therapy ◽  
Clinical Studies ◽  
Innate Immune System ◽  
Innate Immune ◽  
System Response ◽  
Treatment Resistant ◽  
The Impact ◽  
Over Time

Background: Electroconvulsive therapy (ECT) is a powerful and fast-acting anti-depressant strategy, often used in treatment-resistant patients. In turn, patients with treatment-resistant depression often present an increased inflammatory response. The impact of ECT on several pathophysiological mechanisms of depression has been investigated, with a focus which has largely been on cellular and synaptic plasticity. Although changes in the immune system are known to influence neurogenesis, these processes have principally been explored independently from each other in the context of ECT. Objective: The aim of this review was to compare the time-dependent consequences of acute and chronic ECT on concomitant innate immune system and neurogenesis-related outcomes measured in the central nervous system in pre-clinical studies. Results: During the few hours following acute electroconvulsive shock (ECS), the expression of the astrocytic reactivity marker glial fibrillary acidic protein (GFAP) and inflammatory genes, such as cyclooxygenase-2 (COX2), were significantly increased together with the neurogenic brain-derived neurotrophic factor (BDNF) and cell proliferation. Similarly, chronic ECS caused an initial upregulation of the same astrocytic marker, immune genes, and neurogenic factors. Interestingly, over time, inflammation appeared to be dampened, while glial activation and neurogenesis were maintained, after either acute or chronic ECS. Conclusion: Regardless of treatment duration ECS would seemingly trigger a rapid increase in inflammatory molecules, dampened over time, as well as a long-lasting activation of astrocytes and production of growth and neurotrophic factors, leading to cell proliferation. This suggests that both innate immune system response and neurogenesis might contribute to the efficacy of ECT.

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 The Impact of Lactobacillus casei on the Composition of the Cecal Microbiota and Innate Immune System Is Strain Specific

PLoS ONE ◽  
2016 ◽  
Vol 11 (5) ◽  
pp. e0156374 ◽  
Author(s):  
Busra Aktas ◽  
Travis J. De Wolfe ◽  
Nasia Safdar ◽  
Benjamin J. Darien ◽  
James L. Steele
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Lactobacillus Casei ◽  
Innate Immune ◽  
Cecal Microbiota ◽  
The Impact ◽  
Is Strain

scholarly journals Immune cells—A curse and a blessing!

2021 ◽  
Vol 218 (6) ◽  
Author(s):  
Valbona Mirakaj
Keyword(s):  
Cardiovascular Disease ◽  
Immune System ◽  
Immune Cells ◽  
Innate Immune System ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
The Impact

Innate immune cells are crucial in the development and regulation of cardiovascular disease. In this issue, two groups, Davis et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20201839) and Li et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20210008) describe the impact of the innate immune system on the development of cardiovascular disease.

scholarly journals Transcriptomic Analysis of Aedes aegypti Innate Immune System in Response to Ingestion of Chikungunya Virus

2019 ◽  
Vol 20 (13) ◽  
pp. 3133 ◽  
Author(s):  
Liming Zhao ◽  
Barry W. Alto ◽  
Yongxing Jiang ◽  
Fahong Yu ◽  
Yanping Zhang
Keyword(s):  
Immune System ◽  
Virus Infection ◽  
Aedes Aegypti ◽  
Innate Immune System ◽  
Chikungunya Virus ◽  
Innate Immune ◽  
Transcriptomic Analysis ◽  
System Response ◽  
Sequencing Analysis ◽  
Immune System Response

Aedes aegypti (L.) is the primary vector of emergent mosquito-borne viruses, including chikungunya, dengue, yellow fever, and Zika viruses. To understand how these viruses interact with their mosquito vectors, an analysis of the innate immune system response was conducted. The innate immune system is a conserved evolutionary defense strategy and is the dominant immune system response found in invertebrates and vertebrates, as well as plants. RNA-sequencing analysis was performed to compare target transcriptomes of two Florida Ae. aegypti strains in response to chikungunya virus infection. We analyzed a strain collected from a field population in Key West, Florida, and a laboratory strain originating from Orlando. A total of 1835 transcripts were significantly expressed at different levels between the two Florida strains of Ae. aegypti. Gene Ontology analysis placed these genes into 12 categories of biological processes, including 856 transcripts (up/down regulated) with more than 1.8-fold (p-adj (p-adjust value) ≤ 0.01). Transcriptomic analysis and q-PCR data indicated that the members of the AaeCECH genes are important for chikungunya infection response in Ae. aegypti. These immune-related enzymes that the chikungunya virus infection induces may inform molecular-based strategies for interruption of arbovirus transmission by mosquitoes.

scholarly journals Effects of Metal Oxide Nanoparticles on Toll-Like Receptor mRNAs in Human Monocytes

Nanomaterials ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 127 ◽  
Author(s):  
Vladislav A. Vasilichin ◽  
Sergey A. Tsymbal ◽  
Anna F. Fakhardo ◽  
Elizaveta I. Anastasova ◽  
Andrey S. Marchenko ◽  
...  
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Metal Oxide Nanoparticles ◽  
Innate Immune ◽  
Future Research ◽  
System Response ◽  
Widespread Application ◽  
Host Immune Responses ◽  
Immune System Response ◽  
Fragmented Data

For the widespread application of nanotechnology in biomedicine, it is necessary to obtain information about their safety. A critical problem is presented by the host immune responses to nanomaterials. It is assumed that the innate immune system plays a crucial role in the interaction of nanomaterials with the host organism. However, there are only fragmented data on the activation of innate immune system factors, such as toll-like receptors (TLRs), by some nanoparticles (NPs). In this study, we investigated TLRs’ activation by clinically relevant and promising NPs, such as Fe3O4, TiO2, ZnO, CuO, Ag2O, and AlOOH. Cytotoxicity and effects on innate immunity factors were studied in THP-1(Tohoku Hospital Pediatrics-1) cell culture. NPs caused an increase of TLR-4 and -6 expression, which was comparable with the LPS-induced level. This suggests that the studied NPs can stimulate the innate immune system response inside the host. The data obtained should be taken into account in future research and to create safe-by-design biomedical nanomaterials.

The older brain, inflammation, vaccination and the prevention of dementia

2010 ◽  
Vol 20 (4) ◽  
pp. 288-308
Author(s):  
JW Neal
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Therapeutic Potential ◽  
Amyloid Plaque ◽  
Transgenic Animal ◽  
Innate Immune ◽  
Brain Inflammation ◽  
Amyloid Peptide ◽  
System Response ◽  
Protective Function

SummaryAn important protective function of the brain's innate immune system is to detect the presence of proteins such as amyloid and to remove them before they become neurotoxic, as is thought to occur in Alzheimer's disease (AD). Ageing affects the immune system response to infection and can influence the systemic response to vaccination and other potential immunotherapeutic agents. The generation of systemic antibodies is a vital component of the immune response, facilitating the identification and clearance of pathogens from the central nervous system (CNS). Experimental evidence using transgenic animal models of AD has shown successful clearance of amyloid from the CNS following vaccination with an amyloid peptide, and consequently a trial of amyloid beta peptide (Aβ) vaccination was undertaken in older people with AD. This produced some unexpected results, as not only was there evidence for amyloid plaque removal, but also a small number of cases developed encephalitis. A detailed review of the response to vaccination and the neuropathology findings are discussed, showing that the findings are understandable given the effects of ageing upon the innate immune system in the brain. Finally, the therapeutic potential of manipulating the regulatory components of the ageing innate immune system in order to inhibit brain inflammation and reduce cognitive decline is outlined.

4. Making memories

2017 ◽  
pp. 42-55
Author(s):  
Paul Klenerman
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Innate Immune System ◽  
Adaptive Response ◽  
Memory Formation ◽  
Innate Immune ◽  
Over Time

The ability of the immune system to sense pathogens and how they can be targeted specifically needs to be tightly coordinated in space and over time. ‘Making memories’ considers how the immune response develops following exposure to a virus. To make effective memory, the immune response needs to be induced correctly or ‘primed’ during the initial stages of an infection. The first step is for the immune system to develop a response relating to the activation of the innate immune system. Without this, the adaptive response is often subsequently overwhelmed. The mechanics of memory formation and how this is then harnessed in current vaccines are described.

The Impact of Intramedullary Nailing of Tibia Fractures on the Innate Immune System

Shock ◽  
2015 ◽  
Vol 44 (3) ◽  
pp. 209-214 ◽  
Author(s):  
Falco Hietbrink ◽  
Leo Koenderman ◽  
Karlijn J. P. van Wessem ◽  
Luke P. H. Leenen
Keyword(s):  
Immune System ◽  
Intramedullary Nailing ◽  
Innate Immune System ◽  
Innate Immune ◽  
Tibia Fractures ◽  
The Impact
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