scholarly journals Host protection to intestinal worm infections: the importance of activated and armed innate effector cells at the host parasite interface

2020 ◽  
Author(s):  
Anupama Ariyaratne ◽  
Sang Yong Kim ◽  
Stephen M. J. Pollo ◽  
Mayara de Cassia Luzzi ◽  
Joel Bowron ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Serum Antibody ◽  
Parasite Clearance ◽  
Specific Gene ◽  
Alternatively Activated Macrophages ◽  
Effector Cells ◽  
Parasitic Worm ◽  
Parasitic Worms ◽  
Host Parasite

ABSTRACTIntestinal roundworms cause chronic debilitating disease in animals, including humans. A lack of effective vaccines and the emergence of widespread drug resistance only increase the need to better understand parasite clearance mechanisms within the host. Heligmosomoides polygyrus larvae induce a strong intestinal granuloma response within their murine host, which has been associated with resistance. Immune cells, mostly alternatively activated macrophages and eosinophils, accumulate around the tissue encysted parasites to immobilize and damage/kill developing worms. In a one dose (bolus) experimental infection, infected C57Bl/6 mice are unable to clear parasites which results in chronic infection with high worm burdens. However, using a frequent dose trickle model of infection, we, like others, have found that C57Bl/6 mice can clear infection. We found that the clearance is associated with higher granuloma numbers, but no changes in systemic/intestinal Th2 responses. Within the granulomas, we found that myeloid cells had a different transcriptional profile in each of the infected groups, and that high IgG1, but not IgG2c, IgA or IgE, levels were observed around the larvae of only trickle-infected mice. Our results highlight the importance of the granuloma in the host’s ability to clear H. polygyrus and emphasise the need to study this key tissue in more depth, rather than using correlates such as general intestinal or systemic responses.AUTHOR’S SUMMARYDespite decades of research on intestinal parasitic worms, we are still unable to clearly point to why so many people (approximately 1.8 billion) and most livestock/wild animals are infected with these parasites. We have made progress in understanding how the immune system responds to parasitic worms, and how these parasites manipulate our immune system. However, identifying effective clearance mechanisms is complex and context dependent. We have used a model of trickle infection (multiple low doses of parasites) to simulate how people/animals get infected in the real world. Using this model, we have identified the host/parasite interface (the granuloma) within the intestinal tissue to be key in determining the host’s ability to clear worms. Specific gene expression signatures in granuloma immune cells and the presence/absence of antibodies within the granuloma are key factors associated with parasite clearance. Surprisingly, more common identifiers of parasitic worm infections (increased serum antibody levels and/or generalized immune markers) did not associate with protection. These novel findings contribute to a better understanding of the mechanisms underlying effective parasitic worm clearance.

scholarly journals Helminth Glycans at the Host-Parasite Interface and Their Potential for Developing Novel Therapeutics

2022 ◽  
Vol 8 ◽  
Author(s):  
Myrna J. M. Bunte ◽  
Arjen Schots ◽  
Jan E. Kammenga ◽  
Ruud H. P. Wilbers
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Helminth Infection ◽  
Host Immune System ◽  
Lewis X ◽  
Novel Therapeutics ◽  
Antigenic Properties ◽  
Parasitic Worms ◽  
Host Parasite

Helminths are parasitic worms that have successfully co-evolved with their host immune system to sustain long-term infections. Their successful parasitism is mainly facilitated by modulation of the host immune system via the release of excretory-secretory (ES) products covered with glycan motifs such as Lewis X, fucosylated LDN, phosphorylcholine and tyvelose. Evidence is accumulating that these glycans play key roles in different aspects of helminth infection including interactions with immune cells for recognition and evasion of host defences. Moreover, antigenic properties of glycans can be exploited for improving the efficacy of anti-helminthic vaccines. Here, we illustrate that glycans have the potential to open new avenues for the development of novel biopharmaceuticals and effective vaccines based on helminth glycoproteins.

scholarly journals Recognition of tumor cells by Dectin-1 orchestrates innate immune cells for anti-tumor responses

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Shiho Chiba ◽  
Hiroaki Ikushima ◽  
Hiroshi Ueki ◽  
Hideyuki Yanai ◽  
Yoshitaka Kimura ◽  
...  
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Tumor Cells ◽  
Immune Cells ◽  
Innate Immune ◽  
Tumoricidal Activity ◽  
Effector Cells ◽  
Therapeutic Implications ◽  
Tumor Killing

The eradication of tumor cells requires communication to and signaling by cells of the immune system. Natural killer (NK) cells are essential tumor-killing effector cells of the innate immune system; however, little is known about whether or how other immune cells recognize tumor cells to assist NK cells. Here, we show that the innate immune receptor Dectin-1 expressed on dendritic cells and macrophages is critical to NK-mediated killing of tumor cells that express N-glycan structures at high levels. Receptor recognition of these tumor cells causes the activation of the IRF5 transcription factor and downstream gene induction for the full-blown tumoricidal activity of NK cells. Consistent with this, we show exacerbated in vivo tumor growth in mice genetically deficient in either Dectin-1 or IRF5. The critical contribution of Dectin-1 in the recognition of and signaling by tumor cells may offer new insight into the anti-tumor immune system with therapeutic implications.

scholarly journals Immune System Alterations in Multiple Myeloma: Molecular Mechanisms and Therapeutic Strategies to Reverse Immunosuppression

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1353
Author(s):  
Andrea Díaz-Tejedor ◽  
Mauro Lorenzo-Mohamed ◽  
Noemí Puig ◽  
Ramón García-Sanz ◽  
María-Victoria Mateos ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Immune System ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Cytotoxic Effects ◽  
Disease Evolution ◽  
Immune Effector ◽  
Effector Cells ◽  
Surface Molecules ◽  
Immune Effector Cells

Immunosuppression is a common feature of multiple myeloma (MM) patients and has been associated with disease evolution from its precursor stages. MM cells promote immunosuppressive effects due to both the secretion of soluble factors, which inhibit the function of immune effector cells, and the recruitment of immunosuppressive populations. Alterations in the expression of surface molecules are also responsible for immunosuppression. In this scenario, immunotherapy, as is the case of immunotherapeutic monoclonal antibodies (mAbs), aims to boost the immune system against tumor cells. In fact, mAbs exert part of their cytotoxic effects through different cellular and soluble immune components and, therefore, patients’ immunosuppressive status could reduce their efficacy. Here, we will expose the alterations observed in symptomatic MM, as compared to its precursor stages and healthy subjects, in the main immune populations, especially the inhibition of effector cells and the activation of immunosuppressive populations. Additionally, we will revise the mechanisms responsible for all these alterations, including the interplay between MM cells and immune cells and the interactions among immune cells themselves. We will also summarize the main mechanisms of action of the four mAbs approved so far for the treatment of MM. Finally, we will discuss the potential immune-stimulating effects of non-immunotherapeutic drugs, which could enhance the efficacy of immunotherapeutic treatments.

The Immune System Regulation in Sepsis: From Innate to Adaptive

2019 ◽  
Vol 20 (8) ◽  
pp. 799-816 ◽  
Author(s):  
Yue Qiu ◽  
Guo-wei Tu ◽  
Min-jie Ju ◽  
Cheng Yang ◽  
Zhe Luo
Keyword(s):  
Clinical Trials ◽  
Immune System ◽  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Immune Cells ◽  
Current Knowledge ◽  
Systemic Inflammatory Response ◽  
Immune System Regulation

Sepsis, which is a highly heterogeneous syndrome, can result in death as a consequence of a systemic inflammatory response syndrome. The activation and regulation of the immune system play a key role in the initiation, development and prognosis of sepsis. Due to the different periods of sepsis when the objects investigated were incorporated, clinical trials often exhibit negative or even contrary results. Thus, in this review we aim to sort out the current knowledge in how immune cells play a role during sepsis.

scholarly journals The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tian-Yu Lei ◽  
Ying-Ze Ye ◽  
Xi-Qun Zhu ◽  
Daniel Smerin ◽  
Li-Juan Gu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Ischaemic Stroke ◽  
Immune Cells ◽  
Tissue Injury ◽  
Recovery Period ◽  
Vital Functions ◽  
Anti Inflammatory

AbstractThrough considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.

scholarly journals Targeting Transforming Growth Factor β to Enhance Cancer Immunotherapy

2006 ◽  
Vol 13 (4) ◽  
pp. 141-143 ◽  
Author(s):  
T. Hahn ◽  
Emmanuel Akporiaye
Keyword(s):  
Immune System ◽  
Growth Factor ◽  
Cancer Immunotherapy ◽  
Immune Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Human Tumours

Human tumours have evolved intricate mechanisms to evade the immune system, either by avoiding recognition or by inhibiting and eliminating immune cells. [...]

scholarly journals Why Target Innate Immune Cells in Cancers?

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 690
Author(s):  
Mary Poupot
Keyword(s):  
Immune System ◽  
Cancer Cells ◽  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells

The immune system is a smart way to fight cancer, with its precise targeting of cancer cells sparing healthy cells [...]

scholarly journals NCMP-05. DECODING THE IMMUNE SYSTEM RESPONSE TO LEPTOMENINGEAL METASTASIS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii124-ii124
Author(s):  
Jan Remsik ◽  
Xinran Tong ◽  
Ugur Sener ◽  
Danille Isakov ◽  
Yudan Chi ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Leptomeningeal Metastasis ◽  
System Response ◽  
Idle State ◽  
The Central Nervous System ◽  
Health And Disease ◽  
Immune System Response ◽  
Therapeutic Protocols ◽  
Brain And Spinal Cord

Abstract For decades, the central nervous system was considered to be an immune privileged organ with limited access to systemic immunity. However, the leptomeninges, the cerebrospinal fluid (CSF)-filled anatomical structure that protects the brain and spinal cord, represent a relatively immune-rich environment. Despite the presence of immune cells, complications in the CSF, such as infectious meningitis and a neurological development of cancer known as leptomeningeal metastasis, are difficult to treat and are frequently fatal. We show that immune cells entering the CSF are held in an ‘idle’ state that limits their cytotoxic arsenal and antigen presentation machinery. To understand this underappreciated neuroanatomic niche, we used unique mouse models and rare patient samples to characterize its cellular composition and critical signaling events in health and disease at a single-cell resolution. Revealing the mediators of CSF immune response will allow us to re-evaluate current therapeutic protocols and employ rational combinations with immunotherapies, therefore turning the patient’s own immune system into an active weapon against pathogens and cancer.

scholarly journals Role of the immune system in neuropathic pain

2019 ◽  
Vol 20 (1) ◽  
pp. 33-37 ◽  
Author(s):  
Marzia Malcangio
Keyword(s):  
Spinal Cord ◽  
Chronic Pain ◽  
Nervous System ◽  
Neuropathic Pain ◽  
Immune System ◽  
Peripheral Nerve ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Immune Cells ◽  
Peripheral Nerve Injury

AbstractBackgroundAcute pain is a warning mechanism that exists to prevent tissue damage, however pain can outlast its protective purpose and persist beyond injury, becoming chronic. Chronic Pain is maladaptive and needs addressing as available medicines are only partially effective and cause severe side effects. There are profound differences between acute and chronic pain. Dramatic changes occur in both peripheral and central pathways resulting in the pain system being sensitised, thereby leading to exaggerated responses to noxious stimuli (hyperalgesia) and responses to non-noxious stimuli (allodynia).Critical role for immune system cells in chronic painPreclinical models of neuropathic pain provide evidence for a critical mechanistic role for immune cells in the chronicity of pain. Importantly, human imaging studies are consistent with preclinical findings, with glial activation evident in the brain of patients experiencing chronic pain. Indeed, immune cells are no longer considered to be passive bystanders in the nervous system; a consensus is emerging that, through their communication with neurons, they can both propagate and maintain disease states, including neuropathic pain. The focus of this review is on the plastic changes that occur under neuropathic pain conditions at the site of nerve injury, the dorsal root ganglia (DRG) and the dorsal horn of the spinal cord. At these sites both endothelial damage and increased neuronal activity result in recruitment of monocytes/macrophages (peripherally) and activation of microglia (centrally), which release mediators that lead to sensitisation of neurons thereby enabling positive feedback that sustains chronic pain.Immune system reactions to peripheral nerve injuriesAt the site of peripheral nerve injury following chemotherapy treatment for cancer for example, the occurrence of endothelial activation results in recruitment of CX3C chemokine receptor 1 (CX3CR1)-expressing monocytes/macrophages, which sensitise nociceptive neurons through the release of reactive oxygen species (ROS) that activate transient receptor potential ankyrin 1 (TRPA1) channels to evoke a pain response. In the DRG, neuro-immune cross talk following peripheral nerve injury is accomplished through the release of extracellular vesicles by neurons, which are engulfed by nearby macrophages. These vesicles deliver several determinants including microRNAs (miRs), with the potential to afford long-term alterations in macrophages that impact pain mechanisms. On one hand the delivery of neuron-derived miR-21 to macrophages for example, polarises these cells towards a pro-inflammatory/pro-nociceptive phenotype; on the other hand, silencing miR-21 expression in sensory neurons prevents both development of neuropathic allodynia and recruitment of macrophages in the DRG.Immune system mechanisms in the central nervous systemIn the dorsal horn of the spinal cord, growing evidence over the last two decades has delineated signalling pathways that mediate neuron-microglia communication such as P2X4/BDNF/GABAA, P2X7/Cathepsin S/Fractalkine/CX3CR1, and CSF-1/CSF-1R/DAP12 pathway-dependent mechanisms.Conclusions and implicationsDefinition of the modalities by which neuron and immune cells communicate at different locations of the pain pathway under neuropathic pain states constitutes innovative biology that takes the pain field in a different direction and provides opportunities for novel approaches for the treatment of chronic pain.

scholarly journals Arginase in Parasitic Infections: Macrophage Activation, Immunosuppression, and Intracellular Signals

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Cinthia C. Stempin ◽  
Laura R. Dulgerian ◽  
Vanina V. Garrido ◽  
Fabio M. Cerban
Keyword(s):  
Macrophage Activation ◽  
Transforming Growth Factor ◽  
Parasite Clearance ◽  
Alternative Activation ◽  
Parasitic Infections ◽  
Activated Macrophages ◽  
Proinflammatory Response ◽  
Alternatively Activated Macrophages ◽  
Arginase 1

A type 1 cytokine-dependent proinflammatory response inducing classically activated macrophages (CaMϕs) is crucial for parasite control during protozoan infections but can also contribute to the development of immunopathological disease symptoms. Type 2 cytokines such as IL-4 and IL-13 antagonize CaMϕs inducing alternatively activated macrophages (AaMϕs) that upregulate arginase-1 expression. During several infections, induction of arginase-1-macrophages was showed to have a detrimental role by limiting CaMϕ-dependent parasite clearance and promoting parasite proliferation. Additionally, the role of arginase-1 in T cell suppression has been explored recently. Arginase-1 can also be induced by IL-10 and transforming growth factor-β(TGF-β) or even directly by parasites or parasite components. Therefore, generation of alternative activation states of macrophages could limit collateral tissue damage because of excessive type 1 inflammation. However, they affect disease outcome by promoting parasite survival and proliferation. Thus, modulation of macrophage activation may be instrumental in allowing parasite persistence and long-term host survival.

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