RNA N6-Methyladenosine Modifications and the Immune Response

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.

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

PLoS Pathogens ◽

10.1371/journal.ppat.1007437 ◽

2018 ◽

Vol 14 (11) ◽

pp. e1007437 ◽

Cited By ~ 7

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

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00511.2005 ◽

2006 ◽

Vol 291 (6) ◽

pp. R1644-R1650 ◽

Cited By ~ 4

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.

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

Journal of Neuropathology & Experimental Neurology ◽

10.1097/nen.0b013e31817713cc ◽

2008 ◽

Vol 67 (6) ◽

pp. 543-554 ◽

Cited By ~ 5

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

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

PLoS Pathogens ◽

10.1371/journal.ppat.1008345 ◽

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

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

Viruses ◽

10.3390/v12080816 ◽

2020 ◽

Vol 12 (8) ◽

pp. 816 ◽

Cited By ~ 2

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.

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SARS-CoV-2 and interferon blockade

Molecular Medicine ◽

10.1186/s10020-020-00231-w ◽

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.

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Orchestration of Adaptive T Cell Responses by Neutrophil Granule Contents

Mediators of Inflammation ◽

10.1155/2019/8968943 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 6

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.

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Plant Phenolics and Lectins as Vaccine Adjuvants

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666190716110705 ◽

2019 ◽

Vol 20 (15) ◽

pp. 1236-1243 ◽

Cited By ~ 2

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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The Neutrophil’s Role During Health and Disease

Physiological Reviews ◽

10.1152/physrev.00012.2018 ◽

2019 ◽

Vol 99 (2) ◽

pp. 1223-1248 ◽

Cited By ~ 62

Author(s):

Pei Xiong Liew ◽

Paul Kubes

Keyword(s):

Immune Response ◽

Immune Responses ◽

Adaptive Immune Response ◽

Innate Immune ◽

Acute Injury ◽

Complex Cells ◽

Adaptive Immune ◽

Inflammatory Processes ◽

Health And Disease ◽

Injury And Repair

Neutrophils have always been considered as uncomplicated front-line troopers of the innate immune system equipped with limited proinflammatory duties. Yet recently, the role of the neutrophil has been undergoing a rejuvenation of sorts. Neutrophils are now considered complex cells capable of a significant array of specialized functions, and as an effector of the innate immune response, they are able to regulate many processes such as acute injury and repair, cancer, autoimmunity, and chronic inflammatory processes. Furthermore, evidence exists to indicate that neutrophils also contribute to adaptive immunity by aiding the development of specific adaptive immune responses or guiding the subsequent adaptive immune response. With this revived interest in neutrophils and their many novel functions, it is prudent to review what is currently known about neutrophils and, even more importantly, understand what information is lacking. We discuss the essential features of the neutrophil, from its origins, lifespan, subsets, margination and sequestration of the neutrophil to the death of the neutrophil. We highlight neutrophil recruitment to both infected and injured tissues and outline differences in recruitment of neutrophils between different tissues. Finally, we examine how neutrophils use different mechanisms to either bolster protective immune responses or negatively cause pathological outcomes at different locations.

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The Metabolic Phenotype Associated with Mounting an Immune Response to a Systemic Infection of Listeria Monocytogenes (FS12-07-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz049.fs12-07-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Robert Johnson ◽

Adesola Olatunde ◽

Lauren Woodie ◽

Michael Greene ◽

Elizabeth Schwartz

Keyword(s):

Immune Response ◽

Bacterial Infection ◽

Innate Immune Response ◽

Adaptive Immune Response ◽

Innate Immune ◽

Metabolic Phenotype ◽

Metabolic Demand ◽

Pathogen Infection ◽

Full Spectrum ◽

Adaptive Immune

Abstract Objectives Our goal in these studies was to quantitatively determine the metabolic phenotype of intracellular bacterial infection, immune response, and clearance. Mounting an immune response to a bacterial infection is metabolically taxing to the host. During infection, the host exhibits sickness syndrome characterized by fever, lethargy and anorexia. Cells of the immune system also shift cellular metabolic pathways, which alters the metabolic and nutritional needs of the host. Previous studies of the metabolic demands of sickness have used model antigens, mitogens or pattern associated molecular patterns, which do not represent the full spectrum of response to a live pathogen infection. Thus, our study is the first of its kind to assess the full spectrum of metabolic, nutritional, immunological, and behavioral demands of live pathogen infection. Methods Mice were administered either a mock intraperitoneal (ip) injection of PBS (Control) or ip dose of Listeria and individually housed over the course of 12 days in Promethion metabolic cages to monitor their metabolic phenotype. In a parallel study, groups of mice were equivalently treated, yet conventionally housed and sacrificed at 3, 5, 7 and 10 days over the course of infection to determine splenic bacterial burden, Listeria-specific T cell response, and cellular metabolic status. Results We observed that the period of the innate immune response (days 1–4) had the most metabolic demand, indicated by weight loss (P < 0.05), reduced activity (P < 0.05), increased sleep (P < 0.05), and decreased energy expenditure (P < 0.05). During the period of the adaptive immune response (days 5–10), there was little to no metabolic impact in the infected animals when compared to the uninfected control animals. We also observed increased GLUT1 expression (P < 0.05) on the membranes of myeloid cells during the period of highest metabolic demand, indicating shifts in cellular metabolism of innate immune cells during the early stages of infection. Conclusions The innate immune response is more metabolically taxing on the host compared to the adaptive immune response and places an increased metabolic demand on infected animals. Funding Sources Departmental startup funds to Elizabeth Hiltbold Schwartz.

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