scholarly journals Molecular Mechanisms of HIV Immune Evasion of the Innate Immune Response in Myeloid Cells

Viruses ◽  
2012 ◽  
Vol 5 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Mike Mashiba ◽  
Kathleen Collins
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Immune Evasion ◽  
Molecular Mechanisms ◽  
Myeloid Cells ◽  
Innate Immune

scholarly journals Broad Ultrastructural and Transcriptomic Changes Underlie the Multinucleated Giant Hemocyte Mediated Innate Immune Response against Parasitoids

2021 ◽  
pp. 1-20
Author(s):  
Gyöngyi Cinege ◽  
Lilla B. Magyar ◽  
Attila L. Kovács ◽  
Zita Lerner ◽  
Gábor Juhász ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Structural Changes ◽  
Molecular Mechanisms ◽  
Mechanistic Model ◽  
Parasitoid Wasp ◽  
Innate Immune ◽  
Drosophila Ananassae ◽  
Membrane Structures ◽  
Intracytoplasmic Membrane

Multinucleated giant hemocytes (MGHs) represent a novel type of blood cell in insects that participate in a highly efficient immune response against parasitoid wasps involving isolation and killing of the parasite. Previously, we showed that circulating MGHs have high motility and the interaction with the parasitoid rapidly triggers encapsulation. However, structural and molecular mechanisms behind these processes remained elusive. Here, we used detailed ultrastructural analysis and live cell imaging of MGHs to study encapsulation in <i>Drosophila ananassae</i> after parasitoid wasp infection. We found dynamic structural changes, mainly driven by the formation of diverse vesicular systems and newly developed complex intracytoplasmic membrane structures, and abundant generation of giant cell exosomes in MGHs. In addition, we used RNA sequencing to study the transcriptomic profile of MGHs and activated plasmatocytes 72 h after infection, as well as the uninduced blood cells. This revealed that differentiation of MGHs was accompanied by broad changes in gene expression. Consistent with the observed structural changes, transcripts related to vesicular function, cytoskeletal organization, and adhesion were enriched in MGHs. In addition, several orphan genes encoding for hemolysin-like proteins, pore-forming toxins of prokaryotic origin, were expressed at high level, which may be important for parasitoid elimination. Our results reveal coordinated molecular and structural changes in the course of MGH differentiation and parasitoid encapsulation, providing a mechanistic model for a powerful innate immune response.

scholarly journals A multiscale signalling network map of innate immune response in cancer reveals cell heterogeneity signatures

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Maria Kondratova ◽  
Urszula Czerwinska ◽  
Nicolas Sompairac ◽  
Sebastian D. Amigorena ◽  
Vassili Soumelis ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Molecular Mechanisms ◽  
Chemical Species ◽  
Suppressor Cells ◽  
Tumour Microenvironment ◽  
Innate Immune ◽  
Literature Mining ◽  
Cell Type ◽  
Signalling Network

Abstract The lack of integrated resources depicting the complexity of the innate immune response in cancer represents a bottleneck for high-throughput data interpretation. To address this challenge, we perform a systematic manual literature mining of molecular mechanisms governing the innate immune response in cancer and represent it as a signalling network map. The cell-type specific signalling maps of macrophages, dendritic cells, myeloid-derived suppressor cells and natural killers are constructed and integrated into a comprehensive meta map of the innate immune response in cancer. The meta-map contains 1466 chemical species as nodes connected by 1084 biochemical reactions, and it is supported by information from 820 articles. The resource helps to interpret single cell RNA-Seq data from macrophages and natural killer cells in metastatic melanoma that reveal different anti- or pro-tumor sub-populations within each cell type. Here, we report a new open source analytic platform that supports data visualisation and interpretation of tumour microenvironment activity in cancer.

Innate Immune Response to Cytoplasmic DNA: Mechanisms and Diseases

2020 ◽  
Vol 38 (1) ◽  
pp. 79-98 ◽  
Author(s):  
Ming-Ming Hu ◽  
Hong-Bing Shu
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Host Defense ◽  
Cyclic Gmp ◽  
Molecular Mechanisms ◽  
Adaptor Protein ◽  
Innate Immune ◽  
Cellular Stress Response ◽  
Cytoplasmic Dna ◽  
Stress Response Pathway

DNA has been known to be a potent immune stimulus for more than half a century. However, the underlying molecular mechanisms of DNA-triggered immune response have remained elusive until recent years. Cyclic GMP-AMP synthase (cGAS) is a major cytoplasmic DNA sensor in various types of cells that detect either invaded foreign DNA or aberrantly located self-DNA. Upon sensing of DNA, cGAS catalyzes the formation of cyclic GMP-AMP (cGAMP), which in turn activates the ER-localized adaptor protein MITA (also named STING) to elicit the innate immune response. The cGAS-MITA axis not only plays a central role in host defense against pathogen-derived DNA but also acts as a cellular stress response pathway by sensing aberrantly located self-DNA, which is linked to the pathogenesis of various human diseases. In this review, we summarize the spatial and temporal mechanisms of host defense to cytoplasmic DNA mediated by the cGAS-MITA axis and discuss the association of malfunctions of this axis with autoimmune and other diseases.

scholarly journals Vaccinia virus immune evasion: mechanisms, virulence and immunogenicity

2013 ◽  
Vol 94 (11) ◽  
pp. 2367-2392 ◽  
Author(s):  
Geoffrey L. Smith ◽  
Camilla T. O. Benfield ◽  
Carlos Maluquer de Motes ◽  
Michela Mazzon ◽  
Stuart W. J. Ember ◽  
...  
Keyword(s):  
Immune Response ◽  
Vaccinia Virus ◽  
Innate Immune Response ◽  
Immune Evasion ◽  
Mammalian Cells ◽  
Innate Immune ◽  
Gene Encoding ◽  
Cytokines And Chemokines ◽  
Host Innate Immune Response ◽  
New Hosts

Virus infection of mammalian cells is sensed by pattern recognition receptors and leads to an innate immune response that restricts virus replication and induces adaptive immunity. In response, viruses have evolved many countermeasures that enable them to replicate and be transmitted to new hosts, despite the host innate immune response. Poxviruses, such as vaccinia virus (VACV), have large DNA genomes and encode many proteins that are dedicated to host immune evasion. Some of these proteins are secreted from the infected cell, where they bind and neutralize complement factors, interferons, cytokines and chemokines. Other VACV proteins function inside cells to inhibit apoptosis or signalling pathways that lead to the production of interferons and pro-inflammatory cytokines and chemokines. In this review, these VACV immunomodulatory proteins are described and the potential to create more immunogenic VACV strains by manipulation of the gene encoding these proteins is discussed.

The Platelet Glycoprotein Ib-IX Axis In Murine Polymicrobial Sepsis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2274-2274
Author(s):  
Adam Corken ◽  
Susan Russell ◽  
Judith Dent ◽  
Steven Post ◽  
Jerry Ware
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Molecular Mechanisms ◽  
Innate Immune ◽  
Polymicrobial Sepsis ◽  
Platelet Glycoprotein ◽  
Wild Type ◽  
Platelet Receptor ◽  
The Common ◽  
Leucine Rich Repeats

Abstract The platelet glycoprotein (GP) Ib-IX receptor complex is expressed exclusively on the surface of platelets and is well characterized as a primary adhesion receptor supporting normal hemostasis and pathologic thrombosis. Beyond hemostasis and thrombosis, platelets can also participate in the innate immune response and inflammation. While the platelet as a contributor to the immune continuum is recognized, many aspects of the molecular mechanisms whereby platelets influence the immune response are still undefined. Here, we report studies using a murine model of GP Ib-IX deficiency linking GP Ib-IX to the immune response associated with polymicrobial sepsis, as modeled by cecal ligation and puncture (CLP). In the CLP model, genetic absence of the major GP Ib-IX hemostatic ligand, von Willebrand factor (VWF), improves survival following CLP when compared to control wild-type animals (p= 0.003, Logrank analysis). This suggests a VWF role in thrombosis contributes to survival outcome following CLP. In contrast, genetic absence of the VWF platelet receptor, GP Ib-IX, does not improve survival with no statistical difference comparing wild-type animals to GPIb-IX deficient animals. The molecular basis to explain improved survival in VWF-deficient (ligand deficient) but not GPIb-IX deficient (receptor deficient) animals was pursued. We tested the hypothesis GPIb-IX has normal physiologic and pathophysiologic functions beyond platelet adhesion influencing infection and an inflammatory response. Indeed, GPIb-IX influencing the innate immune response is not completely unexpected since a hallmark structural feature of each subunit of the GPIb-IX receptor is leucine rich repeats, the common motif to all members of the toll like receptor family (TLRs). Whether structural similarities are a consequence of ancestral origins for GPIb-IX and TLRs is unknown. We first documented in the absence of murine platelet GP Ib-IX there are reduced platelet-neutrophil and platelet-monocyte interactions under normal conditions and following CLP in whole blood. Whether there are physiologic consequences for disrupting a platelet/monocyte and/or platelet/neutrophil axis was determined via multianalyte profiling of circulating cytokine levels on a Luminex analyzer following CLP. In the absence of GP Ib-IX there is a robust and statistically significant increase 24 hrs following CLP in some of the major proinflammatory cytokines produced by monocytes and macrophages, including TNFα, MCP-1, MIP-β, IL-6, and IL-15. Increases in cytokines, such as IL-5 and IL-13, associated with other immune cells were also observed. These results highlight a coagulation/inflammation interface where the platelet, and specifically GP Ib-IX, contributes to the pathophysiology of CLP. On the one hand, absence of platelet GPIb-IX reduces thrombotic potential, but it occurs at the expense of upregulation of inflammatory cytokine release leading to a reduced survival in CLP. Clearly, survival outcomes in CLP reflect a complex dysregulation of coagulation and inflammation where platelet GPIb-IX likely contributes to both processes with physiologic consequences. Understanding dysregulation of the coagulation/ inflammation interface and identifying a platelet receptor (GPIb-IX) critical to both adds new information to this complex set of pathophysiologic events Sharing the common structural motifs, leucine rich repeats, with the well characterized family of toll-like receptors, platelet GPIb-IX should now be considered an active participant in the inflammatory cascade. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Analysis of the Caenorhabditis elegans innate immune response to Coxiella burnetii

2016 ◽  
Vol 23 (2) ◽  
pp. 111-127 ◽  
Author(s):  
James M Battisti ◽  
Lance A Watson ◽  
Myo T Naung ◽  
Adam M Drobish ◽  
Ekaterina Voronina ◽  
...  
Keyword(s):  
Immune Response ◽  
Caenorhabditis Elegans ◽  
Innate Immune Response ◽  
Coxiella Burnetii ◽  
Molecular Mechanisms ◽  
Q Fever ◽  
Innate Immune ◽  
Human Pathogens ◽  
C Elegans ◽  
Intestinal Distension

The nematode Caenorhabditis elegans is well established as a system for characterization and discovery of molecular mechanisms mediating microbe-specific inducible innate immune responses to human pathogens. Coxiella burnetii is an obligate intracellular bacterium that causes a flu-like syndrome in humans (Q fever), as well as abortions in domesticated livestock, worldwide. Initially, when wild type C. elegans (N2 strain) was exposed to mCherry-expressing C. burnetii (CCB) a number of overt pathological manifestations resulted, including intestinal distension, deformed anal region and a decreased lifespan. However, nematodes fed autoclave-killed CCB did not exhibit these symptoms. Although vertebrates detect C. burnetii via TLRs, pathologies in tol-1(–) mutant nematodes were indistinguishable from N2, and indicate nematodes do not employ this orthologue for detection of C. burnetii. sek-1(–) MAP kinase mutant nematodes succumbed to infection faster, suggesting that this signaling pathway plays a role in immune activation, as previously shown for orthologues in vertebrates during a C. burnetii infection. C. elegans daf-2(–) mutants are hyper-immune and exhibited significantly reduced pathological consequences during challenge. Collectively, these results demonstrate the utility of C. elegans for studying the innate immune response against C. burnetii and could lead to discovery of novel methods for prevention and treatment of disease in humans and livestock.

scholarly journals Enterococcus faecalis Capsular Polysaccharide Serotypes C and D and Their Contributions to Host Innate Immune Evasion

2009 ◽  
Vol 77 (12) ◽  
pp. 5551-5557 ◽  
Author(s):  
Lance R. Thurlow ◽  
Vinai Chittezham Thomas ◽  
Sherry D. Fleming ◽  
Lynn E. Hancock
Keyword(s):  
Immune Response ◽  
Enterococcus Faecalis ◽  
Innate Immune Response ◽  
Immune Evasion ◽  
Capsular Polysaccharide ◽  
Lipoteichoic Acid ◽  
Innate Immune ◽  
Necrosis Factor Alpha ◽  
Host Innate Immune Response ◽  
Innate Immune Evasion

ABSTRACT It has become increasingly difficult to treat infections caused by Enterococcus faecalis due to its high levels of intrinsic and acquired antibiotic resistance. However, few studies have explored the mechanisms that E. faecalis employs to circumvent the host innate immune response and establish infection. Capsular polysaccharides are important virulence factors that are associated with innate immune evasion. We demonstrate, using cultured macrophages (RAW 264.7), that capsule-producing E. faecalis strains of either serotype C or D are more resistant to complement-mediated opsonophagocytosis than unencapsulated strains. We show that differences in opsonophagocytosis are not due to variations in C3 deposition but are due to the ability of capsule to mask bound C3 from detection on the surface of E. faecalis. Similarly, E. faecalis capsule masks lipoteichoic acid from detection, which correlates with decreased tumor necrosis factor alpha production by cultured macrophages in the presence of encapsulated strains compared to that in the presence of unencapsulated strains. Our studies confirm the important role of the capsule as a virulence factor of E. faecalis and provide several mechanisms by which the presence of the capsule influences evasion of the innate immune response and suggest that the capsule could be a potential target for developing alternative therapies to treat E. faecalis infections.

scholarly journals Viral Innate Immune Evasion and the Pathogenesis of Emerging RNA Virus Infections

2019 ◽  
Author(s):  
Tessa Nelemans ◽  
Marjolein Kikkert
Keyword(s):  
Immune Response ◽  
Immune Evasion ◽  
Molecular Mechanisms ◽  
Public Health Problem ◽  
Innate Immune ◽  
Interferon Response ◽  
Replication Capacity ◽  
Human Pathogens ◽  
Emerging Viruses ◽  
Innate Immune Evasion

Positive-sense single-stranded RNA (+ssRNA) viruses comprise many (re-)emerging human pathogens that pose a public health problem. Our innate immune system and in particular the interferon response form the important first line of defense against these viruses. Given their genetic flexibility, these viruses have therefore developed multiple strategies to evade the innate immune response in order to optimize their replication capacity. Already many molecular mechanisms of innate immune evasion by +ssRNA viruses have been identified. However, research addressing the effect of host innate immune evasion on the pathology caused by the viral infection is less prevalent in literature, though very relevant and interesting. Since interferons have been implicated in inflammatory diseases and immunopathology in addition to their protective role in infection, the influence of antagonizing the immune response may have an ambiguous effect on the clinical outcome of the viral disease. Therefore, this review discusses what is currently known about the role of interferons and host immune evasion in the pathogenesis of emerging viruses belonging to the coronaviruses, alphaviruses and flaviviruses.

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