scholarly journals First-in-human demonstration of splenic ultrasound stimulation for non-invasively controlling inflammation

2020 ◽  
Author(s):  
Rachel Stegeman Graham ◽  
Daniel P Zachs ◽  
Victoria Cotero ◽  
Catherine DAgostino ◽  
Despoina Ntiloudi ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Activation ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
B Cell Activation ◽  
Cytokine Release ◽  
Non Invasive ◽  
Adaptive Immune ◽  
Ultrasound Stimulation ◽  
Human Demonstration

Hyperinflammation and uncontrolled cytokine release in infections and autoimmune diseases require therapy to reduce the innate immune response. Here, we present first in-human data showing reduction in pro-inflammatory cytokine release with ultrasound stimulation of the spleen in healthy subjects and in rheumatoid arthritis patients. Single cell RNA sequencing reveals a decrease in IL-1β and IL-8 transcript levels in circulating monocytes. There is also a down regulation of pathways involved in TNF and IL-6 production, and genes regulated by IFN and NFκB. Additional pre-clinical studies reveal that ultrasound can boost B cell activation and antibody production. Splenic ultrasound offers a new non-invasive therapy for treating hyperinflammation without compromising the adaptive immune response

scholarly journals Salmonella escapes adaptive immune response via SIRT2 mediated modulation of innate immune response in dendritic cells

2018 ◽  
Vol 14 (11) ◽  
pp. e1007437 ◽  
Author(s):  
Mayuri Gogoi ◽  
Kasturi Chandra ◽  
Mohsen Sarikhani ◽  
Ramya Ramani ◽  
Nagalingam Ravi Sundaresan ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Innate Immune Response ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Adaptive Immune

scholarly journals RNA N6-Methyladenosine Modifications and the Immune Response

2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Ya-Nan Wang ◽  
Chen-Yang Yu ◽  
Hong-Zhong Jin
Keyword(s):  
Immune Response ◽  
Biological Effects ◽  
Biological Significance ◽  
Adaptive Immune Response ◽  
Noncoding Rnas ◽  
Innate Immune ◽  
Messenger Rnas ◽  
Adaptive Immune ◽  
Wide Range ◽  
Higher Eukaryotes

N6-methyladenosine (m6A) is the most important modification of messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) in higher eukaryotes. Modulation of m6A modifications relies on methyltransferases and demethylases. The discovery of binding proteins confirms that the m6A modification has a wide range of biological effects and significance at the molecular, cellular, and physiological levels. In recent years, techniques for investigating m6A modifications of RNA have developed rapidly. This article reviews the biological significance of RNA m6A modifications in the innate immune response, adaptive immune response, and viral infection.

Changes in immune responses to oxidized LDL epitopes during aging in hypercholesterolemic apoE(−/−) mice

2006 ◽  
Vol 291 (6) ◽  
pp. R1644-R1650 ◽  
Author(s):  
Paul C. Dimayuga ◽  
Xiaoning Zhao ◽  
Juliana Yano ◽  
Kuang-Yuh Chyu
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Time Course ◽  
Oxidized Ldl ◽  
Adaptive Immune Response ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Collagen Content ◽  
Aortic Sinus ◽  
Adaptive Immune

Atherosclerosis is a disease associated with aging and is subject to modulation by both the innate and adaptive immune system. The time course of age-dependent changes in immune regulation in the context of atherosclerosis has not been characterized. This study aims to describe alteration of the immune responses to oxidized LDL (oxLDL) during aging that is associated with changes in plaque size and phenotype in apoE(−/−) mice. Mice fed a Western diet were euthanized at 15–17, 36, or >52 wk of age. The descending aortas were stained for assessment of extent of atherosclerosis. Plaque lipid, macrophage, and collagen content were evaluated in aortic sinus lesions. The adaptive immune response to oxLDL was assessed using anti-malondialdehyde-oxidized LDL (MDA-LDL) and copper-oxidized LDL (Cu-oxLDL) IgG, and the innate immune response was assessed using anti-Cu-oxLDL and phosphorylcholine (PC) IgM. Aging was associated with a significant increase in plaque area and collagen content and a decrease in plaque macrophage and lipid content. MDA-LDL IgG significantly increased at 36 wk but was reduced in mice >52 wk. Cu-oxLDL IgG increased with age and IgG-apoB immune complexes were increased in the >52 wk group. Cu-oxLDL and PC IgM significantly increased with age. The expression of splenic cytokines such as IFN-γ, IL-4, and IL-10 increased with age. Our study shows a generalized increase in innate immune responses associated with progression of atherosclerosis and a less inflammatory and less lipid-containing plaque phenotype during aging. The adaptive immune response appeared to be less generalized, with a specific reduction in MDA-LDL IgG.

scholarly journals The Innate Immune Response to Adjuvants Dictates the Adaptive Immune Response to Autoantigens

2008 ◽  
Vol 67 (6) ◽  
pp. 543-554 ◽  
Author(s):  
Maria A. Staykova ◽  
David Liñares ◽  
Susan A. Fordham ◽  
Judith T. Paridaen ◽  
David O. Willenborg
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Adaptive Immune

scholarly journals Distinct immune responses in patients infected with influenza or SARS-CoV-2, and in COVID-19 survivors, characterised by transcriptomic and cellular abundance differences in blood.

2021 ◽  
Author(s):  
Jelmer Legebeke ◽  
Jenny Lord ◽  
Rebekah Penrice-Randal ◽  
Andres F Vallejo ◽  
Stephen Poole ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell Activation ◽  
Cell Activation ◽  
Topological Analysis ◽  
Adaptive Immune Response ◽  
Influenza Virus Infection ◽  
The Body ◽  
Nucleosome Assembly ◽  
Bioinformatic Tools ◽  
Adaptive Immune

Background The worldwide pandemic caused by SARS-CoV-2 has claimed millions of lives and has had a profound effect on global life. Understanding the pathogenicity of the virus and the body′s response to infection is crucial in improving patient management, prognosis, and therapeutic strategies. To address this, we performed functional transcriptomic profiling to better understand the generic and specific effects of SARS-CoV-2 infection. Methods Whole blood RNA sequencing was used to profile a well characterised cohort of patients hospitalised with COVID-19, during the first wave of the pandemic prior to the availability of approved COVID-19 treatments and who went on to survive or die of COVID-19, and patients hospitalised with influenza virus infection between 2017 and 2019. Clinical parameters between patient groups were compared, and several bioinformatic tools were used to assess differences in transcript abundances and cellular composition. Results The analyses revealed contrasting innate and adaptive immune programmes, with transcripts and cell subsets associated with the innate immune response elevated in patients with influenza, and those involved in the adaptive immune response elevated in patients with COVID-19. Topological analysis identified additional gene signatures that differentiated patients with COVID-19 from patients with influenza, including insulin resistance, mitochondrial oxidative stress and interferon signalling. An efficient adaptive immune response was furthermore associated with patient survival, while an inflammatory response predicted death in patients with COVID-19. A potential prognostic signature was found based on a selection of transcript abundances, associated with circulating immunoglobulins, nucleosome assembly, cytokine production and T cell activation, in the blood transcriptome of COVID-19 patients, upon admission to hospital, which can be used to stratify patients likely to survive or die. Conclusions The results identified distinct immunological signatures between SARS-CoV-2 and influenza, prognostic of disease progression and indicative of different targeted therapies. The altered transcript abundances associated with COVID-19 survivors can be used to predict more severe outcomes in patients with COVID-19.

scholarly journals Correction: Salmonella escapes adaptive immune response via SIRT2 mediated modulation of innate immune response in dendritic cells

2020 ◽  
Vol 16 (2) ◽  
pp. e1008345
Author(s):  
Mayuri Gogoi ◽  
Kasturi Chandra ◽  
Mohsen Sarikhani ◽  
Ramya Ramani ◽  
Nagalingam Ravi Sundaresan ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Innate Immune Response ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Adaptive Immune

scholarly journals Fetal Lymphoid Organ Immune Responses to Transient and Persistent Infection with Bovine Viral Diarrhea Virus

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 816 ◽  
Author(s):  
Katie J. Knapek ◽  
Hanah M. Georges ◽  
Hana Van Campen ◽  
Jeanette V. Bishop ◽  
Helle Bielefeldt-Ohmann ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Innate Immune Response ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Bovine Viral Diarrhea ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Adaptive Immune ◽  
Viral Diarrhea Virus

Bovine Viral Diarrhea Virus (BVDV) fetal infections occur in two forms; persistent infection (PI) or transient infection (TI), depending on what stage of gestation the fetus is infected. Examination of lymphoid organs from both PI and TI fetuses reveals drastically different fetal responses, dependent upon the developmental stage of the fetal immune system. Total RNA was extracted from the thymuses and spleens of uninfected control, PI, and TI fetuses collected on day 190 of gestation to test the hypothesis that BVDV infection impairs the innate and adaptive immune response in the fetal thymus and spleen of both infection types. Transcripts of genes representing the innate immune response and adaptive immune response genes were assayed by Reverse Transcription quatitative PCR (RT-qPCR) (2−ΔΔCq; fold change). Genes of the innate immune response, interferon (IFN) inducible genes, antigen presentation to lymphocytes, and activation of B cells were downregulated in day 190 fetal PI thymuses compared to controls. In contrast, innate immune response genes were upregulated in TI fetal thymuses compared to controls and tended to be upregulated in TI fetal spleens. Genes associated with the innate immune system were not different in PI fetal spleens; however, adaptive immune system genes were downregulated, indicating that PI fetal BVDV infection has profound inhibitory effects on the expression of genes involved in the innate and adaptive immune response. The downregulation of these genes in lymphocytes and antigen-presenting cells in the developing thymus and spleen may explain the incomplete clearance of BVDV and the persistence of the virus in PI animals while the upregulation of the TI innate immune response indicates a more mature immune system, able to clear the virus.

scholarly journals SARS-CoV-2 and interferon blockade

2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Betty Diamond ◽  
Bruce T. Volpe ◽  
Sonya VanPatten ◽  
Yousef Al Abed
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Innate Immune System ◽  
Neutralizing Antibodies ◽  
Cytotoxic T Cells ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Interferon Production ◽  
Therapeutic Implications ◽  
Adaptive Immune

Abstract The response to viral infection generally includes an activation of the adaptive immune response to produce cytotoxic T cells and neutralizing antibodies. We propose that SARS-CoV-2 activates the innate immune system through the renin-angiotensin and kallikrein-bradykinin pathways, blocks interferon production and reduces an effective adaptive immune response. This model has therapeutic implications.

scholarly journals Orchestration of Adaptive T Cell Responses by Neutrophil Granule Contents

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Danielle Minns ◽  
Katie Jane Smith ◽  
Emily Gwyer Findlay
Keyword(s):  
Immune Response ◽  
Immune System ◽  
T Cell ◽  
Innate Immune System ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
T Cell Immunity ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Cell Immunity

Neutrophils are the most abundant leukocytes in peripheral blood and respond rapidly to danger, infiltrating tissues within minutes of infectious or sterile injury. Neutrophils were long thought of as simple killers, but now we recognise them as responsive cells able to adapt to inflammation and orchestrate subsequent events with some sophistication. Here, we discuss how these rapid responders release mediators which influence later adaptive T cell immunity through influences on DC priming and directly on the T cells themselves. We consider how the release of granule contents by neutrophils—through NETosis or degranulation—is one way in which the innate immune system directs the phenotype of the adaptive immune response.

Plant Phenolics and Lectins as Vaccine Adjuvants

2019 ◽  
Vol 20 (15) ◽  
pp. 1236-1243 ◽  
Author(s):  
Hernández-Ramos Reyna-Margarita ◽  
Castillo-Maldonado Irais ◽  
Rivera-Guillén Mario-Alberto ◽  
Ramírez-Moreno Agustina ◽  
Serrano-Gallardo Luis-Benjamín ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Innate Immune Response ◽  
Adaptive Immune Response ◽  
The Body ◽  
Innate Immune ◽  
Vaccine Adjuvants ◽  
Plant Phenolics ◽  
Adaptive Immune ◽  
Foreign Substance

Background: The immune system is responsible for providing protection to the body against foreign substances. The immune system divides into two types of immune responses to study its mechanisms of protection: 1) Innate and 2) Adaptive. The innate immune response represents the first protective barrier of the organism that also works as a regulator of the adaptive immune response, if evaded the mechanisms of the innate immune response by the foreign substance the adaptive immune response takes action with the consequent antigen neutralization or elimination. The adaptive immune response objective is developing a specific humoral response that consists in the production of soluble proteins known as antibodies capable of specifically recognizing the foreign agent; such protective mechanism is induced artificially through an immunization or vaccination. Unfortunately, the immunogenicity of the antigens is an intrinsic characteristic of the same antigen dependent on several factors. Conclusion: Vaccine adjuvants are chemical substances of very varied structure that seek to improve the immunogenicity of antigens. The main four types of adjuvants under investigation are the following: 1) Oil emulsions with an antigen in solution, 2) Pattern recognition receptors activating molecules, 3) Inflammatory stimulatory molecules or activators of the inflammasome complex, and 4) Cytokines. However, this paper addresses the biological plausibility of two phytochemical compounds as vaccine adjuvants: 5) Lectins, and 6) Plant phenolics whose characteristics, mechanisms of action and disadvantages are addressed. Finally, the immunological usefulness of these molecules is discussed through immunological data to estimate effects of plant phenolics and lectins as vaccine adjuvants, and current studies that have implanted these molecules as vaccine adjuvants, demonstrating the results of this immunization.

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