scholarly journals Extracellular Vesicles: Schistosomal Long-Range Precise Weapon to Manipulate the Immune Response

2021 ◽  
Vol 11 ◽  
Author(s):  
Dror Avni ◽  
Orly Avni
Keyword(s):  
Immune Response ◽  
Extracellular Vesicles ◽  
Hygiene Hypothesis ◽  
Innate Immune ◽  
Host Immune System ◽  
Infectious Agents ◽  
Th2 Response ◽  
Selective Targeting ◽  
Th2 Immunity ◽  
Underlying Mechanisms

Schistosomiasis (Bilharziasis), a neglected tropical disease that affects more than 240 million people around the world, is caused by infection with the helminth parasite Schistosoma. As part of their secretome, schistosomes release extracellular vesicles (EVs) that modulate the host immune response. The EV-harbored miRNAs upregulate the innate immune response of the M1 pathway and downregulate the differentiation toward the adaptive Th2 immunity. A schistosomal egg-derived miRNA increases the percentage of regulatory T cells. This schistosomal-inducible immunoediting process generates ultimately a parasitic friendly environment that is applied carefully as restrained Th2 response is crucial for the host survival and successful excretion of the eggs. Evidence indicates a selective targeting of schistosomal EVs, however, the underlying mechanisms are unclear yet. The effects of the schistosomes on the host immune system is in accordance with the hygiene hypothesis, attributing the dramatic increase in recent decades in allergy and other diseases associated with imbalanced immune response, to the reduced exposure to infectious agents that co-evolved with humans during evolution. Deciphering the bioactive cargo, function, and selective targeting of the parasite-secreted EVs may facilitate the development of novel tools for diagnostics and delivered therapy to schistosomiasis, as well as to immune-associated disorders.

CF Monocyte Derived Macrophages Have an Attenuated Response to Extracellular Vesicles Secreted by Airway Epithelial Cells

2021 ◽  
Author(s):  
Katja Koeppen ◽  
Amanda B Nymon ◽  
Roxanna Barnaby ◽  
Zhongyou Li ◽  
Thomas H Hampton ◽  
...  
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Bacterial Infection ◽  
Extracellular Vesicles ◽  
Cell Types ◽  
Airway Epithelial Cells ◽  
Innate Immune ◽  
Airway Epithelial ◽  
Immune Genes ◽  
Innate Immune Genes

Mutations in CFTR alter macrophage responses, for example, by reducing their ability to phagocytose and kill bacteria. Altered macrophage responses may facilitate bacterial infection and inflammation in the lungs, contributing to morbidity and mortality in cystic fibrosis (CF). Extracellular vesicles (EVs) are secreted by multiple cell types in the lungs and participate in the host immune response to bacterial infection, but the effect of EVs secreted by CF airway epithelial cells (AEC) on CF macrophages is unknown. This report examines the effect of EVs secreted by primary AEC on monocyte derived macrophages (MDM) and contrasts responses of CF and WT MDM. We found that EVs generally increase pro-inflammatory cytokine secretion and expression of innate immune genes in MDM, especially when EVs are derived from AEC exposed to Pseudomonas aeruginosa, and that this effect is attenuated in CF MDM. Specifically, EVs secreted by P. aeruginosa exposed AEC induced immune response genes and increased secretion of pro-inflammatory cytokines, chemoattractants and chemokines involved in tissue repair by WT MDM, but these effects were less robust in CF MDM. We attribute attenuated responses by CF MDM to differences between CF and WT macrophages because EVs secreted by CF AEC or WT AEC elicited similar responses in CF MDM. Our findings demonstrate the importance of AEC EVs in macrophage responses and show that the Phe508del mutation in CFTR attenuates the innate immune response of MDM to EVs.

RNA sensors as a mechanism of innate immune evasion among SARS-CoV2, HIV and Nipah viruses

2021 ◽  
Vol 22 ◽  
Author(s):  
Dalia Cicily Kattiparambil Dixon ◽  
Chameli Ratan ◽  
Bhagyalakshmi Nair ◽  
Sabitha Mangalath ◽  
Rachy Abraham ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Innate Immune Response ◽  
Vaccine Development ◽  
Innate Immune ◽  
Interferon Response ◽  
Host Immune System ◽  
Type I ◽  
Adaptive Responses ◽  
Rna Sensors

: Innate immunity is the first line of defence elicited by the host immune system to fight against invading pathogens such as viruses and bacteria. From this elementary immune response, the more complex antigen-specific adaptive responses are recruited to provide a long-lasting memory against the pathogens. Innate immunity gets activated when the host cell utilizes a diverse set of receptors known as pattern recognition receptors (PRR) to recognize the viruses that have penetrated the host and respond with cellular processes like complement system, phagocytosis, cytokine release and inflammation and destruction of NK cells. Viral RNA or DNA or viral intermediate products are recognized by receptors like toll-like receptors(TLRs), nucleotide oligomerization domain(NOD)-like receptors (NLRs) and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) thereby, inducing type I interferon response (IFN) and other proinflammatory cytokines in infected cells or other immune cells. But certain viruses can evade the host innate immune response to replicate efficiently, triggering the spread of the viral infection. The present review describes the similarity in the mechanism chosen by viruses from different families -HIV, SARS-CoV2 and Nipah viruses to evade the innate immune response and how efficiently they establish the infection in the host. The review also addresses the stages of developments of various vaccines against these viral diseases and the challenges encountered by the researchers during vaccine development.

scholarly journals Extracellular Vesicles Deliver Host and Virus RNA and Regulate Innate Immune Response

2017 ◽  
Vol 18 (3) ◽  
pp. 666 ◽  
Author(s):  
Takahisa Kouwaki ◽  
Masaaki Okamoto ◽  
Hirotake Tsukamoto ◽  
Yoshimi Fukushima ◽  
Hiroyuki Oshiumi
Keyword(s):  
Immune Response ◽  
Extracellular Vesicles ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Virus Rna

scholarly journals Subcellular Localizations of RIG-I, TRIM25, and MAVS Complexes

2016 ◽  
Vol 91 (2) ◽  
Author(s):  
M. T. Sánchez-Aparicio ◽  
J. Ayllón ◽  
A. Leo-Macias ◽  
T. Wolff ◽  
A. García-Sastre
Keyword(s):  
Immune Response ◽  
Signaling Pathway ◽  
Stress Granules ◽  
Viral Proteins ◽  
Innate Immune ◽  
Bimolecular Fluorescence Complementation ◽  
Host Immune System ◽  
Type I ◽  
Ns1 Protein ◽  
First Time

ABSTRACT The retinoic acid-inducible gene 1 (RIG-I) signaling pathway is essential for the recognition of viruses and the initiation of host interferon (IFN)-mediated antiviral responses. Once activated, RIG-I interacts with polyubiquitin chains generated by TRIM25 and binds mitochondrial antiviral signaling protein (MAVS), leading to the production of type I IFN. We now show specific interactions among these key partners in the RLR pathway through the use of bimolecular fluorescence complementation (BiFC) and super-resolution microscopy. Dimers of RIG-I, TRIM25, and MAVS localize into different compartments. Upon activation, we show that TRIM25 is redistributed into cytoplasmic dots associated with stress granules, while RIG-I associates with TRIM25/stress granules and with mitochondrial MAVS. In addition, MAVS competes with TRIM25 for RIG-I binding, and this suggests that upon TRIM25-mediated activation of RIG-I, RIG-I moves away from TRIM25 to interact with MAVS at the mitochondria. For the first time, the distribution of these three proteins was analyzed at the same time in virus-infected cells. We also investigated how specific viral proteins modify some of the protein complexes in the pathway. The protease NS3/4A from hepatitis C virus redistributes the complexes RIG-I/MAVS and MAVS/MAVS but not RIG-I/TRIM25. In contrast, the influenza A virus NS1 protein interacts with RIG-I and TRIM25 in specific areas in the cell cytoplasm and inhibits the formation of TRIM25 homocomplexes but not the formation of RIG-I/TRIM25 heterocomplexes, preventing the formation of RIG-I/MAVS complexes. Thus, we have localized spatially in the cell different complexes formed between RIG-I, TRIM25, and MAVS, in the presence or absence of two viral IFN antagonistic proteins. IMPORTANCE The first line of defense against viral infections is the innate immune response. Viruses are recognized by pathogen recognition receptors, such as the RIG-I like receptor family, that activate a signaling cascade that induces IFN production. In the present study, we visualized, for the first time in cells, both in overexpression and endogenous levels, complexes formed among key proteins involved in this innate immune signaling pathway. Through different techniques we were able to analyze how these proteins are distributed and reorganized spatially within the cell in order to transmit the signal, leading to an efficient antiviral state. In addition, this work presents a new means by how, when, and where viral proteins can target these pathways and act against the host immune system in order to counteract the activation of the immune response.

scholarly journals Bacterial lipids: powerful modifiers of the innate immune response

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1334 ◽  
Author(s):  
Courtney E. Chandler ◽  
Robert K. Ernst
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Innate Immune Response ◽  
Lipoteichoic Acid ◽  
Innate Immune ◽  
Microbial Pathogens ◽  
Host Immune System ◽  
Receptor Proteins ◽  
Bacterial Membranes ◽  
Host Innate Immune Response

The innate immune system serves as a first line of defense against microbial pathogens. The host innate immune response can be triggered by recognition of conserved non-self-microbial signature molecules by specific host receptor proteins called Toll-like receptors. For bacteria, many of these molecular triggers reside on or are embedded in the bacterial membrane, the interface exposed to the host environment. Lipids are the most abundant component of membranes, and bacteria possess a unique set of lipids that can initiate or modify the host innate immune response. Bacterial lipoproteins, peptidoglycan, and outer membrane molecules lipoteichoic acid and lipopolysaccharide are key modulators of the host immune system. This review article will highlight some of the research emerging at the crossroads of bacterial membranes and innate immunity.

scholarly journals Synergy between 15-lipoxygenase and secreted PLA2promotes inflammation by formation of TLR4 agonists from extracellular vesicles

2020 ◽  
Vol 117 (41) ◽  
pp. 25679-25689 ◽  
Author(s):  
Van Thai Ha ◽  
Duško Lainšček ◽  
Bernd Gesslbauer ◽  
Eva Jarc-Jovičić ◽  
Tuulia Hyötyläinen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Response ◽  
Extracellular Vesicles ◽  
Acyl Chain ◽  
Innate Immune ◽  
Sterile Inflammation ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Unsaturated Acyl

Damage-associated endogenous molecules induce innate immune response, thus making sterile inflammation medically relevant. Stress-derived extracellular vesicles (stressEVs) released during oxidative stress conditions were previously found to activate Toll-like receptor 4 (TLR4), resulting in expression of a different pattern of immune response proteins in comparison to lipopolysaccharide (LPS), underlying the differences between pathogen-induced and sterile inflammation. Here we report that synergistic activities of 15-lipoxygenase (15-LO) and secreted phospholipase A2(sPLA2) are needed for the formation of TLR4 agonists, which were identified as lysophospholipids (lysoPLs) with oxidized unsaturated acyl chain. Hydroxy, hydroperoxy, and keto products of 2-arachidonoyl-lysoPI oxidation by 15-LO were identified by mass spectrometry (MS), and they activated the same gene pattern as stressEVs. Extracellular PLA2activity was detected in the synovial fluid from rheumatoid arthritis and gout patients. Furthermore, injection of sPLA2promoted K/BxN serum-induced arthritis in mice, whereby ankle swelling was partially TLR4 dependent. Results confirm the role of oxidized lysoPL of stressEVs in sterile inflammation that promotes chronic diseases. Both 15-LO and sPLA2enzymes are induced during inflammation, which opens the opportunity for therapy without compromising innate immunity against pathogens.

scholarly journals Viral Modulation of TLRs and Cytokines and the Related Immunotherapies for HPV-Associated Cancers

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Marconi Rego Barros ◽  
Talita Helena Araújo de Oliveira ◽  
Cristiane Moutinho Lagos de Melo ◽  
Aldo Venuti ◽  
Antonio Carlos de Freitas
Keyword(s):  
Immune Response ◽  
Human Papillomavirus ◽  
Immune System ◽  
Immune Evasion ◽  
Innate Immune System ◽  
Innate Immune ◽  
Cell Maturation ◽  
Host Immune System ◽  
Key Factor ◽  
Infected Cells

The modulation of the host innate immune system is a well-established carcinogenesis feature of several tumors, including human papillomavirus- (HPV-) related cancers. This virus is able to interrupt the initial events of the immune response, including the expression of Toll-like receptors (TLRs), cytokines, and inflammation. Both TLRs and cytokines play a central role in HPV recognition, cell maturation and differentiation as well as immune signalling. Therefore, the imbalance of this sensitive control of the immune response is a key factor for developing immunotherapies, which strengthen the host immune system to accomplish an efficient defence against HPV and HPV-infected cells. Based on this, the review is aimed at exposing the HPV immune evasion mechanisms involving TLRs and cytokines and at discussing existing and potential immunotherapeutic TLR- and cytokine-related tools.

scholarly journals Arthritogenic Alphavirus-Induced Immunopathology and Targeting Host Inflammation as A Therapeutic Strategy for Alphaviral Disease

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 290 ◽  
Author(s):  
Helen Mostafavi ◽  
Eranga Abeyratne ◽  
Ali Zaid ◽  
Adam Taylor
Keyword(s):  
Immune Response ◽  
Therapeutic Strategy ◽  
Current Knowledge ◽  
Symptomatic Relief ◽  
Innate Immune ◽  
Host Immune System ◽  
Inflammatory Drugs ◽  
Global Concern ◽  
Alphavirus Infection

Arthritogenic alphaviruses are a group of medically important arboviruses that cause inflammatory musculoskeletal disease in humans with debilitating symptoms, such as arthralgia, arthritis, and myalgia. The arthritogenic, or Old World, alphaviruses are capable of causing explosive outbreaks, with some viruses of major global concern. At present, there are no specific therapeutics or commercially available vaccines available to prevent alphaviral disease. Infected patients are typically treated with analgesics and non-steroidal anti-inflammatory drugs to provide often inadequate symptomatic relief. Studies to determine the mechanisms of arthritogenic alphaviral disease have highlighted the role of the host immune system in disease pathogenesis. This review discusses the current knowledge of the innate immune response to acute alphavirus infection and alphavirus-induced immunopathology. Therapeutic strategies to treat arthritogenic alphavirus disease by targeting the host immune response are also examined.

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