Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The cytoskeleton in cell-autonomous immunity: structural determinants of host defence.

ABSTRACT: Host cells use antimicrobial proteins, pathogen-restrictive compartmentalization and cell death in their defence against intracellular pathogens. Recent work has revealed that four components of the cytoskeleton--actin, microtubules, intermediate filaments and septins, which are well known for their roles in cell division, shape and movement--have important functions in innate immunity and cellular self-defence. Investigations using cellular and animal models have shown that these cytoskeletal proteins are crucial for sensing bacteria and for mobilizing effector mechanisms to eliminate them. In this Review, we highlight the emerging roles of the cytoskeleton as a structural determinant of cell-autonomous host defence.

SUBMITTER: Mostowy S

PROVIDER: S-EPMC4869833 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

The cytoskeleton in cell-autonomous immunity: structural determinants of host defence.

Mostowy Serge S Shenoy Avinash R AR

Nature reviews. Immunology 20150821 9

Host cells use antimicrobial proteins, pathogen-restrictive compartmentalization and cell death in their defence against intracellular pathogens. Recent work has revealed that four components of the cytoskeleton--actin, microtubules, intermediate filaments and septins, which are well known for their roles in cell division, shape and movement--have important functions in innate immunity and cellular self-defence. Investigations using cellular and animal models have shown that these cytoskeletal p ...[more]

PMID: 26292640

Similar Datasets

An unlikely partnership: parasites, concomitant immunity and host defence.

Project description:Concomitant immunity (CI) against macroparasites describes a state of effective anti-larval immunity coupled with persistent adult infection. Experimental studies indicate that immunologically concealed adult worms might promote anti-larval immunity via the release of cross-reactive antigens, thus creating a barrier against continual infection and restricting burden size within the host. CI offers an important potential benefit to established worms by preventing overcrowding within the host. Thus, CI may be interpreted as akin to vaccination; relatively long-lived adult worms 'vaccinate' their host with larval surface antigens and so benefit from reduced conspecific competition. The shared responsibility for host vaccination among adult worms leads to a problem of collective action. Here, we build on earlier analytical findings about the evolutionary forces that shape cooperation among parasites in order to produce a stochastic simulation model of macroparasite social evolution. First, we theoretically investigate a parasite adaptation hypothesis of CI and demonstrate its plausibility under defined conditions, despite the possibility of evolutionary 'cheats'. Then we derive a set of predictions for testing the hypothesis that CI is partly a host-manipulative parasite adaptation. Evidence in support of this model would present an unusual case of adaptive population regulation.

| S-EPMC1088913 | biostudies-literature

Structural basis for subversion of host cell actin cytoskeleton during Salmonella infection.

Project description:Secreted bacterial type III secretion system (T3SS) proteins are essential for successful infection by many human pathogens. Both T3SS translocator SipC and effector SipA are critical for Salmonella infection by subversion of the host cell cytoskeleton, but the precise molecular interplay between them remains unknown. Here, using cryo-electron microscopy, we show that SipA binds along the F-actin grooves with a unique binding pattern. SipA stabilizes F-actin through charged interface residues and appears to prevent inorganic phosphate release through closure of the "back door" of adenosine 5'-triphosphate pocket. We also show that SipC enhances the binding of SipA to F-actin, thus demonstrating that a sequential presence of T3SS proteins in host cells is associated with a sequence of infection events-starting with actin nucleation, filament growth, and stabilization. Together, our data explain the coordinated interplay of a precisely tuned and highly effective mechanism during Salmonella infection and provide a blueprint for interfering with Salmonella effectors acting on actin.

| S-EPMC10708208 | biostudies-literature

Conservation of Cell Communication Systems in Invertebrate Host-Defence Mechanisms: Possible Role in Immunity and Disease.

Project description:Innate immunity is continuously revealing multiple and highly conserved host-defence mechanisms. Studies on mammalian immunocytes are showing different communication systems that may play a role in coordinating innate immune responses also in invertebrates. Extracellular traps (ETs) are an immune response by which cells release net-like material, including DNA, histones and proteins. ETs are thought to immobilise and kill microorganisms, but are also involved in inflammation and autoimmune disease. Immune cells are also known to communicate through extracellular vesicles secreted in the extracellular environment or exosomes, which can carry a variety of different signalling molecules. Tunnelling nanotubes (TNTs) represent a direct cell-to-cell communication over a long distance, that allow for bi- or uni-directional transfer of cellular components between cells. Their functional role in a number of physio-pathological processes, including immune responses and pathogen transfer, has been underlined. Although ETs, exosomes, and TNTs have been described in invertebrate species, their possible role in immune responses is not fully understood. In this work, available data on these communication systems are summarised, in an attempt to provide basic information for further studies on their relevance in invertebrate immunity and disease.

| S-EPMC7464772 | biostudies-literature

NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens.

Project description:Members of the intracellular nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family contribute to immune responses through activation of nuclear factor-?B (NF-?B), type I interferon and inflammasome signalling. Mice lacking the NLR family member NLRP6 were recently shown to be susceptible to colitis and colorectal tumorigenesis, but the role of NLRP6 in microbial infections and the nature of the inflammatory signalling pathways regulated by NLRP6 remain unclear. Here we show that Nlrp6-deficient mice are highly resistant to infection with the bacterial pathogens Listeria monocytogenes, Salmonella typhimurium and Escherichia coli. Infected Nlrp6-deficient mice had increased numbers of monocytes and neutrophils in circulation, and NLRP6 signalling in both haematopoietic and radioresistant cells contributed to increased susceptibility. Nlrp6 deficiency enhanced activation of mitogen-activated protein kinase (MAPK) and the canonical NF-?B pathway after Toll-like receptor ligation, but not cytosolic NOD1/2 ligation, in vitro. Consequently, infected Nlrp6-deficient cells produced increased levels of NF-?B- and MAPK-dependent cytokines and chemokines. Thus, our results reveal NLRP6 as a negative regulator of inflammatory signalling, and demonstrate a role for this NLR in impeding clearance of both Gram-positive and -negative bacterial pathogens.

| S-EPMC3422416 | biostudies-literature

Alterations in mitochondrial morphology as a key driver of immunity and host defence.

Project description:Mitochondria are dynamic organelles whose architecture changes depending on the cell's energy requirements and other signalling events. These structural changes are collectively known as mitochondrial dynamics. Mitochondrial dynamics are crucial for cellular functions such as differentiation, energy production and cell death. Importantly, it has become clear in recent years that mitochondrial dynamics are a critical control point for immune cell function. Mitochondrial remodelling allows quiescent immune cells to rapidly change their metabolism and become activated, producing mediators, such as cytokines, chemokines and even metabolites to execute an effective immune response. The importance of mitochondrial dynamics in immunity is evident, as numerous pathogens have evolved mechanisms to manipulate host cell mitochondrial remodelling in order to promote their own survival. In this review, we comprehensively address the roles of mitochondrial dynamics in immune cell function, along with modulation of host cell mitochondrial morphology during viral and bacterial infections to facilitate either pathogen survival or host immunity. We also speculate on what the future may hold in terms of therapies targeting mitochondrial morphology for bacterial and viral control.

| S-EPMC8447557 | biostudies-literature

Interleukin (IL)-33: an orchestrator of immunity from host defence to tissue homeostasis.

Project description:Interleukin (IL)-33, a member of the IL-1 superfamily, functions as an alarm signal, which is released upon cell injury or tissue damage to alert the immune system. It has emerged as a chief orchestrator in immunity and has a broad pleiotropic action that influences differentiation, maintenance and function of various immune cell types via the ST2 receptor. Although it has been strongly associated with immunopathology, critically, IL-33 is involved in host defence, tissue repair and homeostasis. In this review, we provide an overview of the signalling pathway of IL-33 and highlight its regulatory functions in immune cells. Furthermore, we attempt a broader discussion of the emerging functions of IL-33 in host defence, tissue repair, metabolism, inflammatory disease and cancer, suggesting potential avenues to manoeuvre IL-33/ST2 signalling as treatment options.

| S-EPMC7299676 | biostudies-literature

Interferon-inducible effector mechanisms in cell-autonomous immunity.

Project description:Interferons (IFNs) induce the expression of hundreds of genes as part of an elaborate antimicrobial programme designed to combat infection in all nucleated cells - a process termed cell-autonomous immunity. As described in this Review, recent genomic and subgenomic analyses have begun to assign functional properties to novel IFN-inducible effector proteins that restrict bacteria, protozoa and viruses in different subcellular compartments and at different stages of the pathogen life cycle. Several newly described host defence factors also participate in canonical oxidative and autophagic pathways by spatially coordinating their activities to enhance microbial killing. Together, these IFN-induced effector networks help to confer vertebrate host resistance to a vast and complex microbial world.

| S-EPMC4150610 | biostudies-literature

PTPN2 elicits cell autonomous and non-cell autonomous effects on antitumor immunity in triple-negative breast cancer.

Project description:The tumor-suppressor PTPN2 is diminished in a subset of triple-negative breast cancers (TNBCs). Paradoxically, PTPN2-deficiency in tumors or T cells in mice can facilitate T cell recruitment and/or activation to promote antitumor immunity. Here, we explored the therapeutic potential of targeting PTPN2 in tumor cells and T cells. PTPN2-deficiency in TNBC associated with T cell infiltrates and PD-L1 expression, whereas low PTPN2 associated with improved survival. PTPN2 deletion in murine mammary epithelial cells TNBC models, did not promote tumorigenicity but increased STAT-1-dependent T cell recruitment and PD-L1 expression to repress tumor growth and enhance the efficacy of anti-PD-1. Furthermore, the combined deletion of PTPN2 in tumors and T cells facilitated T cell recruitment and activation and further repressed tumor growth or ablated tumors already predominated by exhausted T cells. Thus, PTPN2-targeting in tumors and/or T cells facilitates T cell recruitment and/or alleviates inhibitory constraints on T cells to combat TNBC.

| S-EPMC8865802 | biostudies-literature

Intracellular sensing of complement C3 activates cell autonomous immunity.

Project description:Pathogens traverse multiple barriers during infection, including cell membranes. We found that during this transition, pathogens carried covalently attached complement C3 into the cell, triggering immediate signaling and effector responses. Sensing of C3 in the cytosol activated mitochondrial antiviral signaling (MAVS)-dependent signaling cascades and induced proinflammatory cytokine secretion. C3 also flagged viruses for rapid proteasomal degradation, preventing their replication. This system could detect both viral and bacterial pathogens but was antagonized by enteroviruses, such as rhinovirus and poliovirus, which cleave C3 using their 3C protease. The antiviral rupintrivir inhibited 3C protease and prevented C3 cleavage, rendering enteroviruses susceptible to intracellular complement sensing. Thus, complement C3 allows cells to detect and disable pathogens that have invaded the cytosol.

| S-EPMC4172439 | biostudies-literature

Host E3 ubiquitin ligase ITCH mediates <i>Toxoplasma gondii</i> effector GRA35-triggered NLRP1 inflammasome activation and cell-autonomous immunity.

Project description:Toxoplasma gondii is an intracellular parasite that can activate the NLRP1 inflammasome leading to macrophage pyroptosis in Lewis rats, but the underlying mechanism is not well understood. In this study, we performed a genome-wide CRISPR screen and identified the dense granule proteins GRA35, GRA42, and GRA43 as the Toxoplasma effectors mediating cell death in Lewis rat macrophages. GRA35 localizes on the parasitophorous vacuole membrane, where it interacts with the host E3 ubiquitin ligase ITCH. Inhibition of proteasome activity or ITCH knockout prevented pyroptosis in Toxoplasma-infected Lewis rat macrophages, consistent with the "NLRP1 functional degradation model". However, there was no evidence that ITCH directly ubiquitinates or interacts with rat NLRP1. We also found that GRA35-ITCH interaction affected Toxoplasma fitness in IFNγ-activated human fibroblasts, likely due to ITCH's role in recruiting ubiquitin and the parasite-restriction factor RNF213 to the parasitophorous vacuole membrane. These findings identify a new role of host E3 ubiquitin ligase ITCH in mediating effector-triggered immunity, a critical concept that involves recognizing intracellular pathogens and initiating host innate immune responses.

| S-EPMC10760081 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data