Beauveria bassiana Ribotoxin (BbRib) Induces Silkworm Cell Apoptosis via Activating Ros Stress Response

The BbRib gene participates in the infection process of Beauveria bassiana (B. bassiana). It also helps pathogenic fungi to escape and defeat the insect host immune defense system by regulating the innate immune response. However, model insects are rarely used to study the mechanism of fungal ribosomal toxin protein. In this study, BbRib protein was produced by prokaryotic expression and injected into silkworm (Bombyx mori) larvae. The physiological and biochemical indexes of silkworm were monitored, and the pathological effects of BbRib protein on immune tissues of silkworm were examined by Hematoxylin and Eosin (HE) staining. BbRib protein can significantly affect the growth and development of the silkworm, causing poisoning, destroying the midgut and fat body and producing physiological changes. The ROS stress response in the adipose tissue and cells of the silkworm was activated to induce apoptosis. These results indicated that the BbRib gene not only participates in the infection process of B. bassiana, it also helps the pathogenic fungi escape the immune system by regulating the innate immune system of the silkworm, allowing it to break through the silkworm’s immune defense. This study reveals the potential molecular mechanism of BbRib protein to insect toxicity, and provides a theoretical basis and material basis for the development and use of novel insecticidal toxins.

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Effect of plinabulin, a novel late-clinical stage immunotherapeutic agent on the adaptive and innate immune system.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.5_suppl.8 ◽

2020 ◽

Vol 38 (5_suppl) ◽

pp. 8-8

Author(s):

Ramon W. Mohanlal ◽

Lan Huang

Keyword(s):

Immune System ◽

Innate Immune System ◽

Clinical Stage ◽

Onset Time ◽

Immune Defense ◽

Innate Immune ◽

Dependent Manner ◽

Breast Cancer Patients ◽

Post Dose ◽

The Impact

8 Background: Plinabulin (Plin) is a small molecule Dendritic Cell modulator, which in the presence of antigen, increases T-cell proliferation in an antigen-dependent manner marrow. The addition of Plin to Docetaxel (Doc) improved mOS with 4.6 months vs Docetaxel monotherapy, and prolonged DoR with more than 1 year (p < 0.05), which is indicative of an immune-mediated mechanism of action (Mohanlal, ASCO-SITC 2017). Neutrophils are our first line of innate immune defense against foreign invaders. We previously reported that Plinabulin prevents chemotherapy (Chemo) Induced Neutropenia (CIN) in patients receiving Doc or TAC throughout the cycle (Doc, Doxorubicin, Cyclophosphamide) (Blayney ASH 2018, St Gallen 2019). Here we analyzed the onset time of neutrophil increase following Plin administration. In addition, we analyzed the impact of Plin on plasma haptoglobin, which is an acute phase protein with anti-inflammatory effects together with immune-enhancing effects and is an integral part of innate immunity (Kristiansen Nature 2001). Methods: Absolute neutrophil count (ANC) and haptoglobin data were analyzed from Phase 2 study BPI-2358-106 (NCT03294577) with 10 (n = 15), 20 (n = 15) and 30 mg/m2 (n = 12) Plin in Breast Cancer patients receiving TAC. Plin was administered on Day 1. ANC and Haptoglobin were analyzed by a Central Laboratory (Covance), from blood draws at predose, and post-dose Plin at Day 2,3,6,7,8,9,10,11,12,13 and 15, and changes relative to predose value were evaluated. Results: Plin dose-dependently increased ANC within 1 day (P < 0.001) and Haptoglobin within 3 days (P < 0.03) of dosing. Mean haptoglobin (P < 0.0005) and ANC (P < 0.001) levels increased with ~two-fold vs baseline levels. ANC levels remained increased for approximately 1 week and haptoglobin levels for > 3 weeks. Conclusions: Based on Plinabulin’s ability to stimulate the innate system, together with its previously reported evidence as a potent activator of the adaptive immune system (Mohanlal, ASCO-SITC 2017), it is concluded that Plinabulin is a potent stimulator of the adaptive and innate immune system. Clinical trial information: NCT03294577.

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Innate receptors and IL-17 in the immune response against human pathogenic fungi

Revista de la Facultad de Ciencias Médicas de Córdoba ◽

10.31053/1853.0605.v73.n3.13353 ◽

2018 ◽

Vol 73 (3) ◽

Author(s):

María Soledad Miró ◽

Cecilia Vigezzi ◽

Emilse Rodriguez ◽

Paula Alejandra Icely ◽

Juan Pablo Caeiro ◽

...

Keyword(s):

Immune System ◽

Fungal Infections ◽

Pathogenic Fungi ◽

Innate Immune ◽

Special Focus ◽

Medical Interventions ◽

Naturally Occurring ◽

Specific Pathogen ◽

Molecular Patterns ◽

Increased Susceptibility

In recent years, the rise of human fungal infections has been associated to lack of early diagnosis, uneffective antifungal therapies and vaccines. Disturbance in immune homeostasis, which can be caused by medical interventions and immunosuppression induced by disease, are well known as risk factors for these pathologies. Cells of the innate immune system are equipped with surface and cytoplasmic receptors for recognition of microorganisms called pattern recognition receptors (PRRs). PRRs recognize specific pathogen-associated molecular patterns (PAMPs) that are crucial for the activation and killing of pathogenic fungi by immune system. This review will outline the PRRs and cells required for effective antifungal immunity, with a special focus on the major antifungal cytokine IL-17. Finally, naturally occurring human mutations involved in the increased susceptibility to fungal infections are also discussed

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Review of phosphocholine substituents on bacterial pathogen glycans: Synthesis, structures and interactions with host proteins

10.32920/14669052.v1 ◽

2021 ◽

Author(s):

Warren W. Wakarchuk

Keyword(s):

Immune System ◽

Bacterial Pathogen ◽

Adaptive Immune System ◽

Infection Process ◽

Innate Immune ◽

Host Proteins ◽

Adaptive Immune ◽

Carbohydrate Components ◽

Multiple Interactions ◽

Structural Aspects

Among the non-carbohydrate components of glycans, the addition of phosphocholine (ChoP) to the glycans of pathogens occurs more rarely than acetylation or methylation, but it has far more potent biological consequences. These arise from ChoP's multiple interactions with host proteins, which are important at all stages of the infection process. These stages include initial adherence to cells, encountering the host's innate immune system and then the adaptive immune system. Thus, in the initial stages of an infection, ChoP groups are an asset to the pathogen, but they can turn into a disadvantage subsequently. In this review, we have focussed on structural aspects of these phenomena. We describe the biosynthesis of the ChoP modification, the structures of the pathogen glycans known to carry ChoP groups and the host proteins that recognize ChoP.

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Neutrophils—From Bone Marrow to First-Line Defense of the Innate Immune System

Frontiers in Immunology ◽

10.3389/fimmu.2021.767175 ◽

2021 ◽

Vol 12 ◽

Author(s):

Richard Felix Kraus ◽

Michael Andreas Gruber

Keyword(s):

Immune System ◽

Innate Immune System ◽

Current Knowledge ◽

Immune Defense ◽

Innate Immune ◽

Human Organism ◽

Polymorphonuclear Cells ◽

Target Tissue ◽

First Line

Neutrophils (polymorphonuclear cells; PMNs) form a first line of defense against pathogens and are therefore an important component of the innate immune response. As a result of poorly controlled activation, however, PMNs can also mediate tissue damage in numerous diseases, often by increasing tissue inflammation and injury. According to current knowledge, PMNs are not only part of the pathogenesis of infectious and autoimmune diseases but also of conditions with disturbed tissue homeostasis such as trauma and shock. Scientific advances in the past two decades have changed the role of neutrophils from that of solely immune defense cells to cells that are responsible for the general integrity of the body, even in the absence of pathogens. To better understand PMN function in the human organism, our review outlines the role of PMNs within the innate immune system. This review provides an overview of the migration of PMNs from the vascular compartment to the target tissue as well as their chemotactic processes and illuminates crucial neutrophil immune properties at the site of the lesion. The review is focused on the formation of chemotactic gradients in interaction with the extracellular matrix (ECM) and the influence of the ECM on PMN function. In addition, our review summarizes current knowledge about the phenomenon of bidirectional and reverse PMN migration, neutrophil microtubules, and the microtubule organizing center in PMN migration. As a conclusive feature, we review and discuss new findings about neutrophil behavior in cancer environment and tumor tissue.

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Metabolic adjustment of Drosophila hemocyte number and sessility by an adipokine

10.1101/648626 ◽

2019 ◽

Cited By ~ 1

Author(s):

Elodie Ramond ◽

Bianca Petrignani ◽

Jan Paul Dudzic ◽

Jean-Philippe Boquete ◽

Mickaël Poidevin ◽

...

Keyword(s):

Immune System ◽

Blood Cells ◽

Fat Body ◽

Physiological State ◽

Internal Surface ◽

Immune Defense ◽

Peripheral Compartment ◽

Larval Body ◽

Signaling Mechanism ◽

Poor Diet

AbstractIn animals, growth is regulated by the complex interplay between paracrine and endocrine signals. When food is scarce, tissues compete for nutrients, leading to critical resource allocation and prioritization. Little is known about how the immune system maturation is coordinated with the growth of other tissues. Here, we describe a signaling mechanism that regulates the number of hemocytes (blood cells) according to the nutritional state of the Drosophila larva. Specifically, we found that the adipokine NimB5 is produced in the fat body upon nutrient scarcity downstream of metabolic sensors. NimB5 is then secreted and bind to hemocytes to down-regulate their proliferation and adhesion. Blocking this signaling loop results in conditional lethality when larvae are raised on a poor diet, due to excessive hemocyte numbers and insufficient energy storage. Similar regulatory mechanisms shaping the immune system in response to nutrient availability are likely to be widespread in animals.Author summaryDrosophila larval hemocytes (blood cells) are found in two compartments: the lymph gland considered as a reservoir, and the peripheral compartment. Peripheral hemocytes form sessile patches attached to the internal surface of the larval body wall or are found freely circulating in the hemolymph. Little is known about the signals that regulate hemocytes proliferation and localization in the peripheral compartment. In this study, we have identified a new gene, NimrodB5, coding for the NimB5 protein, which is secreted by the fat body and binds to hemocytes. NimB5 inhibits hemocyte proliferation while promoting sessility, leading to an increased number of circulating hemocytes and adhesion defects in NimB5 mutant. We show that nimrodB5 expression by the fat body is controlled by metabolic cues to adjust hemocyte number to the physiological state of the larvae.Interestingly, deregulation of NimB5 causes lethality when larvae are raised on a poor diet due to a defect in regulating hemocytes proliferation. In conclusion, we have identified a new adipokine that optimizes hemocytes number to the physiological state of larvae. Our study also reveals a major role of the fat body in peripheral hematopoiesis regulation and outline how it can be costly to maintain a basal immune defense.

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Tweaking Innate Immunity: The Promise of Innate Immunologicals as Anti-Infectives

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2006/195957 ◽

2006 ◽

Vol 17 (5) ◽

pp. 307-314 ◽

Cited By ~ 8

Author(s):

Kenneth L Rosenthal

Keyword(s):

Innate Immunity ◽

Immune System ◽

Immune Responses ◽

Innate Immune System ◽

Immune Defense ◽

Innate Immune ◽

Parasitic Infections ◽

Type I ◽

Adaptive Immune Responses ◽

Adaptive Immune

New and exciting insights into the importance of the innate immune system are revolutionizing our understanding of immune defense against infections, pathogenesis, and the treatment and prevention of infectious diseases. The innate immune system uses multiple families of germline-encoded pattern recognition receptors (PRRs) to detect infection and trigger a variety of antimicrobial defense mechanisms. PRRs are evolutionarily highly conserved and serve to detect infection by recognizing pathogen-associated molecular patterns that are unique to microorganisms and essential for their survival. Toll-like receptors (TLRs) are transmembrane signalling receptors that activate gene expression programs that result in the production of proinflammatory cytokines and chemokines, type I interferons and antimicrobial factors. Furthermore, TLR activation facilitates and guides activation of adaptive immune responses through the activation of dendritic cells. TLRs are localized on the cell surface and in endosomal/lysosomal compartments, where they detect bacterial and viral infections. In contrast, nucleotide-binding oligomerization domain proteins and RNA helicases are located in the cell cytoplasm, where they serve as intracellular PRRs to detect cytoplasmic infections, particularly viruses. Due to their ability to enhance innate immune responses, novel strategies to use ligands, synthetic agonists or antagonists of PRRs (also known as 'innate immunologicals') can be used as stand-alone agents to provide immediate protection or treatment against bacterial, viral or parasitic infections. Furthermore, the newly appreciated importance of innate immunity in initiating and shaping adaptive immune responses is contributing to our understanding of vaccine adjuvants and promises to lead to improved next-generation vaccines.

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The Role of Innate Immunity in Osteoarthritis: When Our First Line of Defense Goes On the Offensive

The Journal of Rheumatology ◽

10.3899/jrheum.140382 ◽

2015 ◽

Vol 42 (3) ◽

pp. 363-371 ◽

Cited By ~ 101

Author(s):

Eric W. Orlowsky ◽

Virginia Byers Kraus

Keyword(s):

Immune System ◽

Innate Immune System ◽

Defense Mechanisms ◽

Immune Defense ◽

Innate Immune ◽

Low Grade ◽

Wear And Tear ◽

Low Grade Inflammation

Although osteoarthritis (OA) has existed since the dawn of humanity, its pathogenesis remains poorly understood. OA is no longer considered a “wear and tear” condition but rather one driven by proteases where chronic low-grade inflammation may play a role in perpetuating proteolytic activity. While multiple factors are likely active in this process, recent evidence has implicated the innate immune system, the older or more primitive part of the body’s immune defense mechanisms. The roles of some of the components of the innate immune system have been tested in OA modelsin vivoincluding the roles of synovial macrophages and the complement system. This review is a selective overview of a large and evolving field. Insights into these mechanisms might inform our ability to identify patient subsets and give hope for the advent of novel OA therapies.

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Review of phosphocholine substituents on bacterial pathogen glycans: Synthesis, structures and interactions with host proteins

10.32920/14669052 ◽

2021 ◽

Author(s):

Warren W. Wakarchuk

Keyword(s):

Immune System ◽

Bacterial Pathogen ◽

Adaptive Immune System ◽

Infection Process ◽

Innate Immune ◽

Host Proteins ◽

Adaptive Immune ◽

Carbohydrate Components ◽

Multiple Interactions ◽

Structural Aspects

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The coagulation system and its function in early immune defense

Thrombosis and Haemostasis ◽

10.1160/th14-01-0053 ◽

2014 ◽

Vol 112 (10) ◽

pp. 640-648 ◽

Cited By ~ 50

Author(s):

Tom van der Poll ◽

Heiko Herwald

Keyword(s):

Immune System ◽

Infectious Diseases ◽

Blood Coagulation ◽

Innate Immune System ◽

Host Response ◽

Immune Defense ◽

Innate Immune ◽

Coagulation System ◽

High Morbidity ◽

Phylogenetic Studies

SummaryBlood coagulation has a Janus-faced role in infectious diseases. When systemically activated, it can cause serious complications associated with high morbidity and mortality. However, coagulation is also part of the innate immune system and its local activation has been found to play an important role in the early host response to infection. Though the latter aspect has been less investigated, phylogenetic studies have shown that many factors involved in coagulation have ancestral origins which are often combined with anti-microbial features. This review gives a general overview about the most recent advances in this area of research also referred to as immunothrombosis.

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The Squeaky Yeast Gets Greased: The Roles of Host Lipids in the Clearance of Pathogenic Fungi

Journal of Fungi ◽

10.3390/jof6010019 ◽

2020 ◽

Vol 6 (1) ◽

pp. 19

Author(s):

Gaelen Guzman ◽

Patrick Niekamp ◽

Fikadu Geta Tafesse

Keyword(s):

Immune System ◽

Immune Cells ◽

Fungal Pathogens ◽

Fungal Infections ◽

Pathogenic Fungi ◽

Innate Immune ◽

High Morbidity ◽

Human Immune System ◽

Human Immune ◽

Phagocytic Uptake

Fungal infections remain a global health threat with high morbidity and mortality. The human immune system must, therefore, perpetually defend against invasive fungal infections. Phagocytosis is critical for the clearance of fungal pathogens, as this cellular process allows select immune cells to internalize and destroy invading fungal cells. While much is known about the protein players that enable phagocytosis, the various roles that lipids play during this fundamental innate immune process are still being illuminated. In this review, we describe recent discoveries that shed new light on the mechanisms by which host lipids enable the phagocytic uptake and clearance of fungal pathogens.

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