Pre- and Postictal Changes in the Innate Immune System: Cause or Effect?

2021 ◽  
pp. 1-9
Author(s):  
Johannes D. Lang ◽  
David G. Olmes ◽  
Manuel Proske ◽  
Mareike Hagge ◽  
Müjgan Dogan Onugoren ◽  
...  
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Innate Immune System ◽  
Mononuclear Cells ◽  
Sampling Period ◽  
Innate Immune ◽  
Peripheral Blood Mononuclear ◽  
Cytokine Analysis ◽  
Inflammatory Processes ◽  
Active Epilepsy

<b><i>Introduction:</i></b> Recent studies have shown that inflammatory processes might play a role in epileptogenesis. Their role in ictogenesis is much less clear. The aim of this study was to investigate peri-ictal changes of the innate immune system by analyzing changes of immune cells, as well as pro- and anti-inflammatory cytokines. <b><i>Methods:</i></b> Patients with active epilepsy admitted for video-EEG monitoring for presurgical evaluation were included. Blood was sampled every 20 min for 5 h on 3 consecutive days until a seizure occurred. After a seizure, additional samples were drawn immediately, as well as 1 and 24 h later. To analyze the different populations of peripheral blood mononuclear cells, all samples underwent FACS for CD3, CD4, CD8, CD56, CD14, CD16, and CD19. For cytokine analysis, we used a custom bead-based multiplex immunoassay for IFN-γ, IL-1β, IL-1RA, IL-4, IL-6, IL-10, IL-12, IL-17, MCP-1, MIP-1α, and TNFα. <b><i>Results:</i></b> Fourteen patients with focal seizures during the sampling period were included. Natural killer (NK) cells showed a negative correlation (<i>ρ</i> = −0.3362, <i>p</i> = 0.0195) before seizure onset and an immediate increase to 1.95-fold afterward. T helper (<i>T</i><sub>H</sub>) and B cells decreased by 2 and 8%, respectively, in the immediate postictal interval. Nonclassical and intermediate monocytes decreased not until 1 day after the seizures, and cytotoxic T (<i>T</i><sub>C</sub>) cells showed a long-lasting postictal increase by 4%. IL-10 and MCP-1 increased significantly after seizures, and IL-12 decreased in the postictal phase. <b><i>Discussion/Conclusion:</i></b> Our study argues for a role of the innate immune system in the pre- and postictal phases. NK cells might be involved in preictal changes or be altered as an epiphenomenon in the immediate preictal interval.

scholarly journals Characterization of Peripheral Blood Mononuclear Cells Gene Expression Profiles of PediatricStaphylococcus aureusPersistent and Non-Carriers Using a Targeted Assay

2019 ◽  
Author(s):  
Elisabeth Israelsson ◽  
Damien Chaussabel ◽  
Rebecca S.B. Fischer ◽  
Heather C. Moore ◽  
D. Ashley Robinson ◽  
...  
Keyword(s):  
Immune System ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Innate Immune System ◽  
Large Scale ◽  
Mononuclear Cells ◽  
Expression Profiles ◽  
Innate Immune ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

AbstractDefects in innate immunity affect many different physiologic systems and several studies of patients with primary immunodeficiency disorders demonstrated the importance of innate immune system components in disease prevention or colonization of bacterial pathogens. To assess the role of the innate immune system on nasal colonization withStaphylococcus aureus, innate immune responses in pediatricS. aureusnasal persistent carriers (n=15) and non-carriers (n=15) were profiled by analyzing co-clustered gene sets (modules) identified through large-scale transcriptome data analysis as the basis for the development of a targeted assay. We stimulated previously frozen peripheral blood mononuclear cells (PBMCs) from these subjects with i) a panel of TLR ligands, ii) liveS. aureus(either a mixture of strains or stimulation with respective carriage isolates), or iii) heat-killedS. aureus. We found no difference in responses between carriers and non-carriers when PBMCs were stimulated with a panel of TLR ligands. However, PBMCs stimulated with liveS. aureuselicited a significantly different response that also differed from the response elicited following stimulation with deadS. aureus. Furthermore, we observed a distinct stimulation profile for PBMCs isolated from persistent carriers stimulated with their respective live or dead carriage strains compared to responses observed for PBMCs isolated from non-carriers that were similar regardless of whether or not the bacteria were alive or not. These data suggested that innate pathway signaling is different between persistent and non-carriers ofS. aureus.

scholarly journals Toll-like receptors and hypertension

2014 ◽  
Vol 307 (5) ◽  
pp. R501-R504 ◽  
Author(s):  
Madhu V. Singh ◽  
François M. Abboud
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Expression Patterns ◽  
Adaptor Proteins ◽  
Nuclear Factor Κb ◽  
Innate Immune ◽  
Toll Like Receptors ◽  
Cardiovascular Damage ◽  
Inflammatory Processes ◽  
Molecular Patterns

Hypertension and associated inflammatory processes that accelerate cardiovascular damage are regulated by the innate immune system. Toll-like receptors (TLR) are major components of the innate immune system that recognize endogenous damage-associated molecular patterns to activate prominent inflammatory signaling including activation of nuclear factor-κB (NF-κB). However, the role of TLR in the etiology of hypertension is not well understood. TLR signaling is dependent on adaptor proteins that, along with the TLR expression patterns, confer specificity of the inflammatory response and its pathological targets. Here we review the conceptual framework of how TLR and their adaptor proteins may differentially affect hypertension and cardiac hypertrophy by different stimuli.

scholarly journals NK Cell Memory to Cytomegalovirus: Implications for Vaccine Development

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 394
Author(s):  
Calum Forrest ◽  
Ariane Gomes ◽  
Matthew Reeves ◽  
Victoria Male
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Innate Immune System ◽  
Vaccine Development ◽  
Nk Cell ◽  
Innate Immune ◽  
Lymphoid Cells ◽  
Murine Cytomegalovirus ◽  
Immune Memory ◽  
Cell Memory

Natural killer (NK) cells are innate lymphoid cells that recognize and eliminate virally-infected and cancerous cells. Members of the innate immune system are not usually considered to mediate immune memory, but over the past decade evidence has emerged that NK cells can do this in several contexts. Of these, the best understood and most widely accepted is the response to cytomegaloviruses, with strong evidence for memory to murine cytomegalovirus (MCMV) and several lines of evidence suggesting that the same is likely to be true of human cytomegalovirus (HCMV). The importance of NK cells in the context of HCMV infection is underscored by the armory of NK immune evasion genes encoded by HCMV aimed at subverting the NK cell immune response. As such, ongoing studies that have utilized HCMV to investigate NK cell diversity and function have proven instructive. Here, we discuss our current understanding of NK cell memory to viral infection with a focus on the response to cytomegaloviruses. We will then discuss the implications that this will have for the development of a vaccine against HCMV with particular emphasis on how a strategy that can harness the innate immune system and NK cells could be crucial for the development of a vaccine against this high-priority pathogen.

scholarly journals Understanding the Role of Innate Immune Cells and Identifying Genes in Breast Cancer Microenvironment

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2226
Author(s):  
Israa Shihab ◽  
Bariaa A. Khalil ◽  
Noha Mousaad Elemam ◽  
Ibrahim Y. Hachim ◽  
Mahmood Yaseen Hachim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Tumor Microenvironment ◽  
Nk Cells ◽  
Immune Cells ◽  
Innate Immune System ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Cancer Microenvironment

The innate immune system is the first line of defense against invading pathogens and has a major role in clearing transformed cells, besides its essential role in activating the adaptive immune system. Macrophages, dendritic cells, NK cells, and granulocytes are part of the innate immune system that accumulate in the tumor microenvironment such as breast cancer. These cells induce inflammation in situ by secreting cytokines and chemokines that promote tumor growth and progression, in addition to orchestrating the activities of other immune cells. In breast cancer microenvironment, innate immune cells are skewed towards immunosuppression that may lead to tumor evasion. However, the mechanisms by which immune cells could interact with breast cancer cells are complex and not fully understood. Therefore, the importance of the mammary tumor microenvironment in the development, growth, and progression of cancer is widely recognized. With the advances of using bioinformatics and analyzing data from gene banks, several genes involved in NK cells of breast cancer individuals have been identified. In this review, we discuss the activities of certain genes involved in the cross-talk among NK cells and breast cancer. Consequently, altering tumor immune microenvironment can make breast tumors more responsive to immunotherapy.

scholarly journals Bcr and Abr Cooperate in Negatively Regulating Acute Inflammatory Responses

2009 ◽  
Vol 29 (21) ◽  
pp. 5742-5750 ◽  
Author(s):  
Jess M. Cunnick ◽  
Sabine Schmidhuber ◽  
Gang Chen ◽  
Min Yu ◽  
Sun-Ju Yi ◽  
...  
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Inflammatory Responses ◽  
Small Gtpase ◽  
Innate Immune ◽  
Ros Production ◽  
Activated Neutrophils ◽  
Inflammatory Processes ◽  
Null Mutant Mice

ABSTRACT Bcr and Abr are GTPase-activating proteins for the small GTPase Rac. Both proteins are expressed in cells of the innate immune system, including neutrophils and macrophages. The function of Bcr has been linked to the negative regulation of neutrophil reactive oxygen species (ROS) production, but the function of Abr in the innate immune system was unknown. Here, we report that mice lacking both proteins are severely affected in two models of experimental endotoxemia, including exposure to Escherichia coli lipopolysaccharide and polymicrobial sepsis, with extensive microvascular leakage, resulting in severe pulmonary edema and hemorrhage. Additionally, in vivo-activated neutrophils of abr and bcr null mutant mice produced excessive tissue-damaging myeloperoxidase (MPO), elastase, and ROS. Moreover, the secretion of the tissue metalloproteinase MMP9 by monocytes and ROS by elicited macrophages was abnormally high. In comparison, ROS production from bone marrow monocytes was not significantly different from that of controls, and the exocytosis of neutrophil secondary and tertiary granule products, including lactoferrin, was normal. These data show that Abr and Bcr normally curb very specific functions of mature tissue innate immune cells, and that each protein has distinct as well as partly overlapping functions in the downregulation of inflammatory processes.

scholarly journals Potent Stimulation of the Innate Immune System by aLeishmania brasiliensis Recombinant Protein

2001 ◽  
Vol 69 (9) ◽  
pp. 5270-5277 ◽  
Author(s):  
Monamaris M. Borges ◽  
Antonio Campos-Neto ◽  
Paul Sleath ◽  
Keneth H. Grabstein ◽  
Philip J. Morrissey ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Immune System ◽  
Nk Cells ◽  
Innate Immune System ◽  
Reticuloendothelial System ◽  
Scid Mice ◽  
Innate Immune ◽  
Initiation Factor ◽  
Interleukin 12 ◽  
Microbial World

ABSTRACT The interaction of the innate immune system with the microbial world involves primarily two sets of molecules generally known as microbial pattern recognition receptors and microbial pattern recognition molecules, respectively. Examples of the former are the Toll receptors present particularly in macrophages and dendritic cells. Conversely, the microbial pattern recognition molecules are conserved protist homopolymers, such as bacterial lipopolysaccharides, lipoteichoic acids, peptidoglycans, glucans, mannans, unmethylated bacterial DNA, and double-strand viral RNA. However, for protists that lack most of these molecules, such as protozoans, the innate immune system must have evolved receptors that recognize other groups of microbial molecules. Here we present evidence that a highly purified protein encoded by a Leishmania brasiliensis gene may be one such molecule. This recombinant leishmanial molecule, a homologue of eukaryotic ribosomal elongation and initiation factor 4a (LeIF), strongly stimulates spleen cells from severe combined immunodeficient (SCID) mice to produce interleukin-12 (IL-12), IL-18, and high levels of gamma interferon. In addition, LeIF potentiates the cytotoxic activity of the NK cells of these animals. Because LeIF is a conserved molecule and because SCID mice lack T and B lymphocytes but have a normal innate immune system (normal reticuloendothelial system and NK cells), these results suggest that proteins may also be included as microbial pattern recognition molecules. The nature of the receptor involved in this innate recognition is unknown. However, it is possible to exclude the Toll receptor Tlr4 as a putative LeIF receptor because the gene encoding this receptor is defective in C3H/HeJ mice, the mouse strain used in the present studies.

scholarly journals The Memories of NK Cells: Innate-Adaptive Immune Intrinsic Crosstalk

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Sara Gabrielli ◽  
Claudio Ortolani ◽  
Genny del Zotto ◽  
Francesca Luchetti ◽  
Barbara Canonico ◽  
...  
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Innate Immune System ◽  
Adaptive Immune System ◽  
Point Of View ◽  
Innate Immune ◽  
Adaptive Immune ◽  
System A ◽  
Evolutionary Point

Although NK cells are considered part of the innate immune system, a series of evidences has demonstrated that they possess characteristics typical of the adaptive immune system. These NK adaptive features, in particular their memory-like functions, are discussed from an ontogenetic and evolutionary point of view.

scholarly journals Impact of brief exercise on peripheral blood NK cell gene and microRNA expression in young adults

2013 ◽  
Vol 114 (5) ◽  
pp. 628-636 ◽  
Author(s):  
Shlomit Radom-Aizik ◽  
Frank Zaldivar ◽  
Fadia Haddad ◽  
Dan M. Cooper
Keyword(s):  
Nk Cells ◽  
Mirna Expression ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Nk Cell ◽  
In Silico Analysis ◽  
Innate Immune ◽  
Peripheral Blood Mononuclear ◽  
Ergometer Exercise ◽  
Cell Gene

Natural killers (NK) cells are unique innate immune cells that increase up to fivefold in the circulating blood with brief exercise and are known to play a key role in first-response defense against pathogens and cancer immunosurveillance. Whether exercise alters NK cell gene and microRNA (miRNA) expression is not known. Thirteen healthy men (20–29 yr old) performed ten 2-min bouts of cycle ergometer exercise at a constant work equivalent to an average of 77% of maximum O2 consumption interspersed with 1-min rest. Blood was drawn before and immediately after the exercise challenge. NK cells were isolated from peripheral blood mononuclear cells using a negative magnetic cell separation method. We used Affymetrix U133+2.0 arrays for gene expression and Agilent Human miRNA V2 Microarray for miRNAs. A stringent statistical approach (false discovery rate < 0.05) was used to determine that exercise significantly altered the expression of 986 genes and 23 miRNAs. Using in silico analysis, we found exercise-related gene pathways where there was a high likelihood of gene-miRNA interactions. These pathways were predominantly associated with cancer and cell communication, including p53 signaling pathway, melanoma, glioma, prostate cancer, adherens junction, and focal adhesion. These data support the hypothesis that exercise affects the gene and miRNA expression pattern in the population of NK cells in the circulation and suggest mechanisms through which physical activity could alter health through the innate immune system.

The role of Natural killer (NK) cells as APCs, Cytotoxicity, Immuno-regulatory in Innate and Adaptive immune as Potential Therapeutic and Preventive Target in Infectious Diseases

2021 ◽  
Vol 12 (04) ◽  
pp. 415-437
Author(s):  
Dr. Zelalem Kiros Bitsue
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Natural Killer ◽  
Host Defense ◽  
Immune Regulation ◽  
Innate Immune System ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Adaptive Immune

Natural killer (NK) cells are lymphocytes of the innate immune system that are critical in host defense and immune regulation. They are activated or inhibited through the ligation of germline-encoded receptors and are involved in mediating cytotoxicity, in producing cytokines and in providing co-stimulation to cells of the adaptive immune system.

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