scholarly journals The Natterin Proteins Diversity: A Review on Phylogeny, Structure, and Immune Function

Toxins ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 538
Author(s):  
Carla Lima ◽  
Geonildo Rodrigo Disner ◽  
Maria Alice Pimentel Falcão ◽  
Ana Carolina Seni-Silva ◽  
Adolfo Luis Almeida Maleski ◽  
...  
Keyword(s):  
Immune Cells ◽  
Intracellular Signaling ◽  
First Record ◽  
Immune Defense ◽  
Innate Immune ◽  
Defense System ◽  
Signaling Mechanisms ◽  
Wide Range ◽  
Sequence Similarities ◽  
Jawless Fish

Since the first record of the five founder members of the group of Natterin proteins in the venom of the medically significant fish Thalassophryne nattereri, new sequences have been identified in other species. In this work, we performed a detailed screening using available genome databases across a wide range of species to identify sequence members of the Natterin group, sequence similarities, conserved domains, and evolutionary relationships. The high-throughput tools have enabled us to dramatically expand the number of members within this group of proteins, which has a remote origin (around 400 million years ago) and is spread across Eukarya organisms, even in plants and primitive Agnathans jawless fish. Overall, the survey resulted in 331 species presenting Natterin-like proteins, mainly fish, and 859 putative genes. Besides fish, the groups with more species included in our analysis were insects and birds. The number and variety of annotations increased the knowledge of the obtained sequences in detail, such as the conserved motif AGIP in the pore-forming loop involved in the transmembrane barrel insertion, allowing us to classify them as important constituents of the innate immune defense system as effector molecules activating immune cells by interacting with conserved intracellular signaling mechanisms in the hosts.

scholarly journals Elucidating the Innate Immunological Effects of Mild Magnetic Hyperthermia on U87 Human Glioblastoma Cells: An in vitro Study

2021 ◽  
Author(s):  
Stefano Persano ◽  
Francesco Vicini ◽  
Alessandro Poggi ◽  
Jordi Leonardo Castrillo Fernandez ◽  
Giusy Maria Rita Rizzo ◽  
...  
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Nk Cell ◽  
Magnetic Hyperthermia ◽  
Innate Immune ◽  
Target Cells ◽  
Innate Immune Cells ◽  
Glioblastoma Cells ◽  
Mild Hyperthermia ◽  
Wide Range

Cancer immunotherapies are gaining a large popularity and many of them have been approved as standard second-line or in some cases even as first-line treatment for a wide range of cancers. However, immunotherapy has not shown a clinically relevant success in glioblastoma (GBM), principally due to the brain’s “immune-privileged” status and the peculiar tumor microenvironment (TME) of GBM featured by lack of presence of tumor-infiltrating lymphocytes and the establishment of immunosuppressive mechanisms. Emerging evidence has highlighted the key role played by innate immune cells in immunosurveillance and in initiating and driving immune responses against GBM. Immunogenic cell death (ICD) is a promising approach to elicit direct activation of the innate immune system by inducing in target cancer cells the expression of molecular signatures recognized through a repertoire of innate immune cell pattern recognition receptors (PRRs) by effector innate immune cells. Herein, we explored local mild thermal treatment, generated by using ultrasmall (size ~ 17 nm) cubic-shaped iron oxide nanoparticles exposed to an external alternating magnetic field (AMF), to induce ICD in U87 glioblastoma cells. In accordance with what has been previously observed with other types of tumors, we found that mild hyperthermia modulates the immunological profile of U87 glioblastoma cells by inducing stress-associated signals leading to enhanced phagocytosis and killing of U87 cells by macrophages. Finally, we demonstrated that mild magnetic hyperthermia has a modulatory effect on the expression of inhibitory and activating NK cell ligands on target cells. Interestingly, alteration in the expression of NK ligands, caused by mild hyperthermia treatment, in U87 glioblastoma cells, increased their susceptibility to NK cell killing and NK cell functionality. The overall findings demonstrate that mild magnetic hyperthermia stimulates ICD and sensitizes GBM cells to NK-mediated killing by inducing the upregulation of specific stress ligands, providing a novel immunotherapeutic approach for GBM treatment, with potential to synergize with existing NK cell-based therapies thus improving their therapeutic outcomes.

scholarly journals Fetal-Derived Immune Cells at the Roots of Lifelong Pathophysiology

2021 ◽  
Vol 9 ◽  
Author(s):  
Elvira Mass ◽  
Rebecca Gentek
Keyword(s):  
Immune Cells ◽  
Innate Immune ◽  
Hematopoietic Stem ◽  
Environmental Perturbations ◽  
Wide Range ◽  
Range Of Functions ◽  
Health And Disease ◽  
Fetal Hematopoiesis ◽  
Early Life Events

Tissue-resident innate immune cells exert a wide range of functions in both adult homeostasis and pathology. Our understanding of when and how these cellular networks are established has dramatically changed with the recognition that many lineages originate at least in part from fetal sources and self-maintain independently from hematopoietic stem cells. Indeed, fetal-derived immune cells are found in most organs and serous cavities of our body, where they reside throughout the entire lifespan. At the same time, there is a growing appreciation that pathologies manifesting in adulthood may be caused by adverse early life events, a concept known as “developmental origins of health and disease” (DOHaD). Yet, whether fetal-derived immune cells are mechanistically involved in DOHaD remains elusive. In this review, we summarize our knowledge of fetal hematopoiesis and its contribution to adult immune compartments, which results in a “layered immune system.” Based on their ontogeny, we argue that fetal-derived immune cells are prime transmitters of long-term consequences of prenatal adversities. In addition to increasing disease susceptibility, these may also directly cause inflammatory, degenerative, and metabolic disorders. We explore this notion for cells generated from erythro-myeloid progenitors (EMP) produced in the extra-embryonic yolk sac. Focusing on macrophages and mast cells, we present emerging evidence implicating them in lifelong disease by either somatic mutations or developmental programming events resulting from maternal and early environmental perturbations.

scholarly journals Plant Antimicrobial Peptides as Potential Anticancer Agents

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Jaquelina Julia Guzmán-Rodríguez ◽  
Alejandra Ochoa-Zarzosa ◽  
Rodolfo López-Gómez ◽  
Joel E. López-Meza
Keyword(s):  
Antimicrobial Peptides ◽  
Anticancer Agents ◽  
Pathogenic Bacteria ◽  
Defense Mechanism ◽  
Immune Defense ◽  
Innate Immune ◽  
High Morbidity ◽  
Anticancer Activities ◽  
Innate Immune Defense ◽  
Wide Range

Antimicrobial peptides (AMPs) are part of the innate immune defense mechanism of many organisms and are promising candidates to treat infections caused by pathogenic bacteria to animals and humans. AMPs also display anticancer activities because of their ability to inactivate a wide range of cancer cells. Cancer remains a cause of high morbidity and mortality worldwide. Therefore, the development of methods for its control is desirable. Attractive alternatives include plant AMP thionins, defensins, and cyclotides, which have anticancer activities. Here, we provide an overview of plant AMPs anticancer activities, with an emphasis on their mode of action, their selectivity, and their efficacy.

Innate immune defense system of the skin

2013 ◽  
Vol 24 (1) ◽  
pp. 32-e9 ◽  
Author(s):  
Maryam Afshar ◽  
Richard L. Gallo
Keyword(s):  
Immune Defense ◽  
Innate Immune ◽  
Defense System ◽  
Innate Immune Defense

Natural killer cell in the developing life

2015 ◽  
Vol 43 (1) ◽  
Author(s):  
Yen-Chang Lee ◽  
Syh-Jae Lin
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Immune Cells ◽  
Killer Cell ◽  
Immune Defense ◽  
Innate Immune ◽  
First Line ◽  
Successful Pregnancy ◽  
Neonatal Stage

AbstractNatural killer (NK) cells that provide first-line innate immune reactions against virus-infected and tumor cells have different roles in different body sites and in different stages. From the beginning of life, NK cells participate in many aspects of development, especially in a successful pregnancy and a healthy neonatal stage. This article reviews recent advances regarding the role of NK cells in implantation, placentation and immune tolerance during pregnancy as well as in the neonatal immune defense. The interactions between NK cells and other immune cells in each developmental stage are discussed.

scholarly journals Stretching the Function of Innate Immune Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Erica M. Orsini ◽  
Apostolos Perelas ◽  
Brian D. Southern ◽  
Lisa M. Grove ◽  
Mitchell A. Olman ◽  
...  
Keyword(s):  
Immune Cells ◽  
Human Disease ◽  
Intracellular Signaling ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Innate Immune ◽  
Transient Receptor Potential Vanilloid ◽  
Innate Immune Cells ◽  
Mechanical Stimuli ◽  
Sense And Respond

The importance of innate immune cells to sense and respond to their physical environment is becoming increasingly recognized. Innate immune cells (e.g. macrophages and neutrophils) are able to receive mechanical signals through several mechanisms. In this review, we discuss the role of mechanosensitive ion channels, such as Piezo1 and transient receptor potential vanilloid 4 (TRPV4), and cell adhesion molecules, such as integrins, selectins, and cadherins in biology and human disease. Furthermore, we explain that these mechanical stimuli activate intracellular signaling pathways, such as MAPK (p38, JNK), YAP/TAZ, EDN1, NF-kB, and HIF-1α, to induce protein conformation changes and modulate gene expression to drive cellular function. Understanding the mechanisms by which immune cells interpret mechanosensitive information presents potential targets to treat human disease. Important areas of future study in this area include autoimmune, allergic, infectious, and malignant conditions.

scholarly journals Interleukin-22 Influences the Th1/Th17 Axis

2021 ◽  
Vol 12 ◽  
Author(s):  
Hannes Lindahl ◽  
Tomas Olsson
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Inflammatory Diseases ◽  
Adaptive Immune System ◽  
Cell Polarization ◽  
The Body ◽  
Innate Immune ◽  
Interleukin 22 ◽  
Downstream Effects ◽  
Wide Range

Interleukin-22 (IL-22) is secreted by a wide range of immune cells and its downstream effects are mediated by the IL-22 receptor, which is present on non-immune cells in many organs throughout the body. IL-22 is an inflammatory mediator that conditions the tissue compartment by upregulating innate immune responses and is also a homeostatic factor that promotes tissue integrity and regeneration. Interestingly, the IL-22 system has also been linked to many T cell driven inflammatory diseases. Despite this, the downstream effects of IL-22 on the adaptive immune system has received little attention. We have reviewed the literature for experimental data that suggest IL-22 mediated effects on T cells, either transduced directly or via mediators expressed by innate immune cells or non-immune cells in response to IL-22. Collectively, the reviewed data indicate that IL-22 has a hitherto unappreciated influence on T helper cell polarization, or the secretion of signature cytokines, that is context dependent but in many cases results in a reduction of the Th1 type response and to some extent promotion of regulatory T cells. Further studies are needed that specifically address these aspects of IL-22 signaling, which can benefit the understanding and treatment of a wide range of diseases.

Viral Antigens Trigger Granzyme B Secretion by Human CD5+ B1 Cells in the Presence of Interleukin 21.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4729-4729
Author(s):  
Kai Sontheimer ◽  
Sue Blackwell ◽  
Magdalena Hagn ◽  
Verena Ebel ◽  
Thamara Beyer ◽  
...  
Keyword(s):  
Nk Cells ◽  
Conflicts Of Interest ◽  
Granzyme B ◽  
Elevated Serum ◽  
Immune Defense ◽  
Innate Immune ◽  
Viral Antigens ◽  
Wide Range ◽  
Interleukin 21 ◽  
B1 Cells

Abstract Abstract 4729 CD5+ B1 cells are thought to play a key role in innate immune responses by producing and secreting natural immunoglobulins, which bind to a wide range of bacterial, viral antigens as well as auto-antigens. Here we demonstrate that B1 cells from human cord blood are able to express the pro-apoptotic serine protease granzyme B (GrB) in response to viruses including tick-borne encephalitis virus, rabies virus, and hepatitis B virus. Using pharmacological tools we reveal that this response depends on B cell receptor stimulation, toll-like receptor 9 engagement and interleukin 21 (IL-21), a cytokine primarily found in the acute phase of viral infections. While up to 35% of freshly isolated B1 cells directly respond with GrB expression to stimulation with inactivated viruses in the presence of IL-21, similar, though lower reactions in CD5- B2 cells are only found after, but not before vaccination of the donor against the respective virus. Of note, GrB-expressing B1 cells feature a homogeneous CD19+CD5+GrB+CD20+CD27-CD38-IgD- phenotype and B1 cell-derived GrB is secreted in an enzymatically active state, reaching levels comparable to those secreted by activated cytotoxic cells. GrB induction requires activation of similar signaling pathways as in CTL and NK cells including members of the JAK/STAT pathway. Our findings suggest GrB secretion by B1 cells represents a novel innate immune response mechanism. GrB-secreting B1 cells may play a role in early anti-viral immune defense, and may contribute to elevated serum GrB levels found in various viral diseases. Further studies will elucidate whether CD5+ B1 cells, possibly in co-operation with NK cells, exhibit cytotoxicity towards virus-infected as well as tumor cells. Disclosures: No relevant conflicts of interest to declare.

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