scholarly journals Innovation in NLR and TLR sensing drives the MHC-II free Atlantic cod immune system

2020 ◽  
Author(s):  
Xingkun Jin ◽  
Bernat Morro ◽  
Ole K. Tørresen ◽  
Visila Moiche ◽  
Monica H. Solbakken ◽  
...  
Keyword(s):  
Immune System ◽  
Mhc Class Ii ◽  
Atlantic Cod ◽  
Ex Vivo ◽  
Specific Cell ◽  
Major Response ◽  
History Of ◽  
Underlying Mechanisms ◽  
Molecular Patterns ◽  
Cluster Of Differentiation

AbstractThe genome sequencing of Atlantic cod revealed an immune system absent of specific cell surface toll-like receptors (TLRs), major histocompatibility complex (MHC) class II, invariant chain (CD74) and the CD4 (cluster of differentiation 4) receptor. Despite the loss of these major components considered as critical to vertebrate innate and adaptive immune systems the cod system is fully functional, however the underlying mechanisms of the immune response in cod remain largely unknown. In this study, ex vivo cod macrophages were challenged with various bacterial and viral microbe-associated molecular patterns (MAMP) to identify major response pathways. Cytosolic MAMP-PRR pathways based upon the NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs) were identified as the critical response pathways. Our analyses suggest that internalization of exogenous ligands through scavenger receptors drives both pathways activating transcription factors like NF-kB (Nuclear factor-kappa B) and interferon regulatory factors (IRFs). Further, ligand-dependent differential expression of a unique TLR25 isoform and multiple NLR paralogues suggests (sub)neofunctionalisation toward specific immune defensive strategies. Our results further demonstrate that the unique immune system of the Atlantic cod provides an unprecedented opportunity to explore the evolutionary history of PRR-based signalling in vertebrate immunity.

scholarly journals Innovation in Nucleotide-Binding Oligomerization-Like Receptor and Toll-Like Receptor Sensing Drives the Major Histocompatibility Complex-II Free Atlantic Cod Immune System

2020 ◽  
Vol 11 ◽  
Author(s):  
Xingkun Jin ◽  
Bernat Morro ◽  
Ole K. Tørresen ◽  
Visila Moiche ◽  
Monica H. Solbakken ◽  
...  
Keyword(s):  
Immune System ◽  
Mhc Class Ii ◽  
Atlantic Cod ◽  
Ex Vivo ◽  
Major Response ◽  
History Of ◽  
Pathogen Recognition Receptors ◽  
Underlying Mechanisms ◽  
Class Ii Antigen ◽  
Molecular Patterns

The absence of MHC class II antigen presentation and multiple pathogen recognition receptors in the Atlantic cod has not impaired its immune response however how underlying mechanisms have adapted remains largely unknown. In this study, ex vivo cod macrophages were challenged with various bacterial and viral microbe-associated molecular patterns (MAMP) to identify major response pathways. Cytosolic MAMP-PRR pathways based upon the NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs) were identified as the critical response pathways. Our analyses suggest that internalization of exogenous ligands through scavenger receptors drives both pathways activating transcription factors like NF-kB (Nuclear factor-kappa B) and interferon regulatory factors (IRFs). Further, ligand-dependent differential expression of a unique TLR25 isoform and multiple NLR paralogues suggests (sub)neofunctionalization toward specific immune defensive strategies. Our results further demonstrate that the unique immune system of the Atlantic cod provides an unprecedented opportunity to explore the evolutionary history of PRR-based signaling in vertebrate immunity.

scholarly journals Uncovering the underlying mechanism of cancer tumorigenesis and development under an immune microenvironment from global quantification of the landscape

2017 ◽  
Vol 14 (131) ◽  
pp. 20170105 ◽  
Author(s):  
Li Wenbo ◽  
Jin Wang
Keyword(s):  
Immune System ◽  
Global Sensitivity Analysis ◽  
Underlying Mechanism ◽  
Specific Cell ◽  
Combination Immunotherapy ◽  
Immune Microenvironment ◽  
Recovery Processes ◽  
Cancer Immunity ◽  
Underlying Mechanisms ◽  
Equilibrium Phases

The study of the cancer–immune system is important for understanding tumorigenesis and the development of cancer and immunotherapy. In this work, we build a comprehensive cancer–immune model including both cells and cytokines to uncover the underlying mechanism of cancer immunity based on landscape topography. We quantify three steady-state attractors, normal state, low cancer state and high cancer state, for the innate immunity and adaptive immunity of cancer. We also illustrate the cardinal inhibiting cancer immunity interactions and promoting cancer immunity interactions through global sensitivity analysis. We simulate tumorigenesis and the development of cancer and classify these into six stages. The characteristics of the six stages can be classified further into three groups. These correspond to the escape, elimination and equilibrium phases in immunoediting, respectively. Under specific cell–cell interactions strength oscillations emerge. We found that tumorigenesis and cancer recovery processes may need to go through cancer–immune oscillation, which consumes more energy. Based on the cancer–immune landscape, we predict three types of cells and two types of cytokines for cancer immunotherapy as well as combination immunotherapy. This landscape framework provides a quantitative way to understand the underlying mechanisms of the interplay between cancer and the immune system for cancer tumorigenesis and development.

scholarly journals Specific modulation of the root immune system by a community of commensal bacteria

2021 ◽  
Vol 118 (16) ◽  
pp. e2100678118
Author(s):  
Paulo J. P. L. Teixeira ◽  
Nicholas R. Colaianni ◽  
Theresa F. Law ◽  
Jonathan M. Conway ◽  
Sarah Gilbert ◽  
...  
Keyword(s):  
Immune System ◽  
Commensal Bacteria ◽  
Immunomodulatory Activity ◽  
Specific Cell ◽  
Bacterial Flagellum ◽  
Surface Receptors ◽  
Evolutionarily Conserved ◽  
Type 3 Secretion System ◽  
Molecular Patterns ◽  
Type 3

Plants have an innate immune system to fight off potential invaders that is based on the perception of nonself or modified-self molecules. Microbe-associated molecular patterns (MAMPs) are evolutionarily conserved microbial molecules whose extracellular detection by specific cell surface receptors initiates an array of biochemical responses collectively known as MAMP-triggered immunity (MTI). Well-characterized MAMPs include chitin, peptidoglycan, and flg22, a 22-amino acid epitope found in the major building block of the bacterial flagellum, FliC. The importance of MAMP detection by the plant immune system is underscored by the large diversity of strategies used by pathogens to interfere with MTI and that failure to do so is often associated with loss of virulence. Yet, whether or how MTI functions beyond pathogenic interactions is not well understood. Here we demonstrate that a community of root commensal bacteria modulates a specific and evolutionarily conserved sector of the Arabidopsis immune system. We identify a set of robust, taxonomically diverse MTI suppressor strains that are efficient root colonizers and, notably, can enhance the colonization capacity of other tested commensal bacteria. We highlight the importance of extracellular strategies for MTI suppression by showing that the type 2, not the type 3, secretion system is required for the immunomodulatory activity of one robust MTI suppressor. Our findings reveal that root colonization by commensals is controlled by MTI, which, in turn, can be selectively modulated by specific members of a representative bacterial root microbiota.

PERAN IBU DALAM PENINGKATAN SISTEM IMUN ANAK DENGAN INFEKSI SALURAN PERNAFASAN AKUT

2019 ◽  
Vol 11 (2) ◽  
pp. 79-86
Author(s):  
Cindy Ayustin Noya ◽  
Angkit Kinasih ◽  
Venti Agustina ◽  
R.Rr Maria Dyah Kurniasari
Keyword(s):  
Immune System ◽  
Acute Respiratory Infection ◽  
Lower Respiratory Tract ◽  
Research Method ◽  
Respiratory Infections ◽  
Acute Respiratory Infections ◽  
Clean Environment ◽  
History Of ◽  
Qualitative Descriptive

Infeksi saluran pernafasan akut atau yang sering disebut ISPA merupakan infeksi pada saluran pernafasan baik saluran pernafasan atas atau bawah.ISPA juga kebanyakan terjadi pada anak balita karena daya tahan tubuh mereka tidak kuat dalam menghadapi penyakit ISPA. ISPA mengakibatkan kematiansekitar15%-20% per tahun pada usia balita di Negara berkembang. Tujuan penelitian ini adalah untuk mengetahui dan menganalisa peran ibu dalam meningkatkan sistem imun anak dengan ISPA.Metode penelitian yang digunakan dalam penelitian ini adalah kualitatif deskriptif dengan sampel purposive sampling.Populasi dan sampel penelitian ini adalah ibu yang mempunyai anak dengan riwayat dan saat ini menderita penyakit ISPA di Batu Gajah Kota Ambon.Partisipan dalam penelitian ini berjumlah 5 orang. Hasil dari penelitian mendapati 4 kategori yaitu pemberian nutrisi pada anak untuk memenuhi kebutuhan agar sistem imunnya terjaga, kebersihan lingkungan, peran ibu dalam melakukan pencegahan pada anaknya yang mengalami ISPA, dan  peran ibu dalam menjaga dan mempertahankan kesehatan anaknya.   Kata kunci: peran ibu, sistem imun, ispa THE ROLE OF MOTHERS IN INCREASING IMMUNE SYSTEM OF CHILDREN WITH ACUTE RESPIRATORY INFECTION    ABSTRACT Acute respiratory infections or often called ARI is an infection of the upper or lower respiratory tract. ARI occurs mostly in children under the age of five because their endurance is not strong in dealing with ARI. ARI results in deaths of around 15%-20% per year at the age of under-five in developing countries. The purpose of this study was to determine and analyze the role of mothers in improving the immune system of children against ARI. The research method used in this study was qualitative descriptive with a purposive sampling sample. Respondents and samples of this study were five mothers who had children with a history of ARI and currently suffering from the disease in Batu Gajah, Ambon City. The results of the study found 4 categories, namely providing nutrition to children to meet their needs so that their immune systems are maintained, clean environment, mother's role in preventing children with ARI, and mother's role to preserve and maintain the health of their children. The findings indicated that in terms of coping or improving the immune system of a child to avoid ARI, it is necessary to have role the of mothers in providing nutrition so that the immune system is boosted, besides that the mother can prevent and protect her child from various diseases, especially ARI. Keywords: role of mothers, immune system, acute respiratory infections

XMODULATION IN MICEAND MEN: IL-10 PRODUCING CELLS INBLOOD AND LYMPHOID TISSUE

2008 ◽  
Vol 31 (4) ◽  
pp. 3
Author(s):  
L Barrett ◽  
M Grant ◽  
R Liwski ◽  
K West
Keyword(s):  
Immune System ◽  
Peripheral Blood ◽  
Lymphoid Tissue ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
White Blood Cells ◽  
Interleukin 10 ◽  
Healthy Individuals ◽  
Human Immune System ◽  
Healthy Humans

Background: The human immune system provides remarkable protection from a plethora of pathogens, but can cause damage when activated for a prolonged time (as inpersistent infections) or against self (autoimmunity). Therefore, mechanisms of immune system downregulation and control are imperative. There is little data on how the immune system is controlled in healthy individuals. We recently described a novel population of white blood cells that constitutively produce the immunomodulatory cytokine interleukin-10 (IL-10). Our objective was to further delineate the distribution of these cells in human and mouse models, as well as potential triggers for interleukin-10 production in vitro. Methods: Human and animal protocols were reviewed and approved by the institutional ethics board and animal care facilities, and informed consent was obtained from all human donors. The ex vivo percentage of peripheral blood CD36^+IL-10^+ mononuclear cells was assessed by intracellular flow cytometry in 10 healthy individuals. IL-10 production after exposure to twoCD36 ligands, thrombospondin and oxidized low density lipoprotein (oxLDL) was measured at 8 hours. Peripheral blood mononuclear cells and splenocytes from BL/6 (n=5) and Balb/c (n=1) micewere assessed for CD36^+IL-10^+ cells ex vivo as well. Results: The percentage of CD36^+IL-10^+ cells in peripheral blood fromhealthy individuals ranges between 0.1% and 0.9%. The percentage was similar in mouse peripheral blood, with a range of 0.4%-1.1%. These cells were also found in mouse spleen at a higher frequency than peripherally (1.1-1.5%). Human CD36^+IL-10^+ cells have more IL-10 when exposed to thrombospondin, oxLDL. Conclusions: Our novel population of IL-10 producing cells is found not only in healthy humans, but also in lymphoid tissue and blood from pathogen free mice. This highlights the evolutionary conservation of the cell across species, and suggests an important homeostatic function. The physiologic ligands for CD36 are ubiquitous in circulation, and ourin vitro data suggests a link between CD36 ligation and IL-10 production. IL-10 is a known immune system modulator, and its production by these cells may help maintain homeostaticcontrol of the immune system.

scholarly journals Chronic low-level cadmium exposure in rats affects cytokine production by activated T cells

2019 ◽  
Vol 8 (2) ◽  
pp. 227-237 ◽  
Author(s):  
Alexandra E. Turley ◽  
Joseph W. Zagorski ◽  
Rebekah C. Kennedy ◽  
Robert A. Freeborn ◽  
Jenna K. Bursley ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Low Dose ◽  
Cytokine Production ◽  
Ex Vivo ◽  
Cadmium Exposure ◽  
Activated T Cells ◽  
Low Level

The purpose of this study was to determine the effect of subchronic, oral, low-dose cadmium exposure (32 ppm over 10 weeks) on the rat immune system. We found that cadmium exposure increased the induction of IFNγ and IL-10 in T cells activated ex vivo after cadmium exposure.

scholarly journals Release mechanisms of major DAMPs

APOPTOSIS ◽  
2021 ◽  
Vol 26 (3-4) ◽  
pp. 152-162
Author(s):  
Atsushi Murao ◽  
Monowar Aziz ◽  
Haichao Wang ◽  
Max Brenner ◽  
Ping Wang
Keyword(s):  
Rna Binding ◽  
High Mobility ◽  
Live Cells ◽  
Membrane Channel ◽  
Membrane Rupture ◽  
Underlying Mechanisms ◽  
Shock Proteins ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Secretory Lysosomes

AbstractDamage-associated molecular patterns (DAMPs) are endogenous molecules which foment inflammation and are associated with disorders in sepsis and cancer. Thus, therapeutically targeting DAMPs has potential to provide novel and effective treatments. When establishing anti-DAMP strategies, it is important not only to focus on the DAMPs as inflammatory mediators but also to take into account the underlying mechanisms of their release from cells and tissues. DAMPs can be released passively by membrane rupture due to necrosis/necroptosis, although the mechanisms of release appear to differ between the DAMPs. Other types of cell death, such as apoptosis, pyroptosis, ferroptosis and NETosis, can also contribute to DAMP release. In addition, some DAMPs can be exported actively from live cells by exocytosis of secretory lysosomes or exosomes, ectosomes, and activation of cell membrane channel pores. Here we review the shared and DAMP-specific mechanisms reported in the literature for high mobility group box 1, ATP, extracellular cold-inducible RNA-binding protein, histones, heat shock proteins, extracellular RNAs and cell-free DNA.

scholarly journals Quantifying fluorescent glycan uptake to elucidate strain-level variability in foraging behaviors of rumen bacteria

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Leeann Klassen ◽  
Greta Reintjes ◽  
Jeffrey P. Tingley ◽  
Darryl R. Jones ◽  
Jan-Hendrik Hehemann ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Ex Vivo ◽  
Rapid Assessment ◽  
Vital Role ◽  
Strain Level ◽  
Metabolic Phenotype ◽  
Specific Cell ◽  
Bacterial Cells ◽  
Carbohydrate Utilization

AbstractGut microbiomes, such as the microbial community that colonizes the rumen, have vast catabolic potential and play a vital role in host health and nutrition. By expanding our understanding of metabolic pathways in these ecosystems, we will garner foundational information for manipulating microbiome structure and function to influence host physiology. Currently, our knowledge of metabolic pathways relies heavily on inferences derived from metagenomics or culturing bacteria in vitro. However, novel approaches targeting specific cell physiologies can illuminate the functional potential encoded within microbial (meta)genomes to provide accurate assessments of metabolic abilities. Using fluorescently labeled polysaccharides, we visualized carbohydrate metabolism performed by single bacterial cells in a complex rumen sample, enabling a rapid assessment of their metabolic phenotype. Specifically, we identified bovine-adapted strains of Bacteroides thetaiotaomicron that metabolized yeast mannan in the rumen microbiome ex vivo and discerned the mechanistic differences between two distinct carbohydrate foraging behaviors, referred to as “medium grower” and “high grower.” Using comparative whole-genome sequencing, RNA-seq, and carbohydrate-active enzyme fingerprinting, we could elucidate the strain-level variability in carbohydrate utilization systems of the two foraging behaviors to help predict individual strategies of nutrient acquisition. Here, we present a multi-faceted study using complimentary next-generation physiology and “omics” approaches to characterize microbial adaptation to a prebiotic in the rumen ecosystem.

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