scholarly journals Location, Location, Location: Is Membrane Partitioning Everything When It Comes to Innate Immune Activation?

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Martha Triantafilou ◽  
Philipp M. Lepper ◽  
Robin Olden ◽  
Ivo de Seabra Rodrigues Dias ◽  
Kathy Triantafilou
Keyword(s):  
Plasma Membrane ◽  
Immune System ◽  
Lipid Rafts ◽  
Immune Activation ◽  
Innate Immune System ◽  
Innate Immune ◽  
Membrane Microdomains ◽  
General View ◽  
Immune Recognition ◽  
Innate Immune Activation

In the last twenty years, the general view of the plasma membrane has changed from a homogeneous arrangement of lipids to a mosaic of microdomains. It is currently thought that islands of highly ordered saturated lipids and cholesterol, which are laterally mobile, exist in the plane of the plasma membrane. Lipid rafts are thought to provide a means to explain the spatial segregation of certain signalling pathways emanating from the cell surface. They seem to provide the necessary microenvironment in order for certain specialised signalling events to take place, such as the innate immune recognition. The innate immune system seems to employ germ-lined encoded receptors, called pattern recognition receptors (PRRs), in order to detect pathogens. One family of such receptors are the Toll-like receptors (TLRs), which are the central “sensing” apparatus of the innate immune system. In recent years, it has become apparent that TLRs are recruited into membrane microdomains in response to ligands. These nanoscale assemblies of sphingolipid, cholesterol, and TLRs stabilize and coalesce, forming signalling platforms, which transduce signals that lead to innate immune activation. In the current paper, we will investigate all past and current literature concerning recruitment of extracellular and intracellular TLRs into lipid rafts and how this membrane organization modulates innate immune responses.

scholarly journals CD46 Plays a Key Role in Tailoring Innate Immune Recognition of Apoptotic and Necrotic Cells

2005 ◽  
Vol 280 (43) ◽  
pp. 36342-36354 ◽  
Author(s):  
Kristina Elward ◽  
Mark Griffiths ◽  
Masashi Mizuno ◽  
Claire L. Harris ◽  
Jim W. Neal ◽  
...  
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Apoptotic Cell ◽  
Membrane Attack Complex ◽  
Factor H ◽  
Innate Immune ◽  
Immune Recognition ◽  
Alternative Pathways ◽  
Complement Regulator ◽  
Complement C1q

Complement is the canonical innate immune system involved in host defense and tissue repair with the clearance of cell debris. In contrast to the robust armory mounted against microbial nonself-pathogens, complement is selectively activated on altered self (i.e. apoptotic and necrotic cells) to instruct the safe demise by poorly characterized mechanisms. Our data shed new light on the role of complement C1q in sensing nucleic acids (NA) rapidly exposed on apoptotic Jurkat T cell membranes and in driving C3 opsonization but without the lytic membrane attack complex. DNA/RNase-treated apoptotic cells failed to activate complement. We found that several other apoptotic cell models, including senescent keratinocytes, ionophore-treated sperm cells, and CMK-derived platelets, stained for cleaved caspase 3 were rapidly losing the key complement regulator CD46. CD46 from nuclear and membrane stores was found to cluster into blebs and shed into microparticles together with NA, phosphatidylserine, C1q, and factor H. Classical and alternative pathways of complement were involved in the recognition of H2O2-treated necrotic cells. Membrane attack complex was detected on necrotic cells possibly as a result of CD46 and CD59 shedding into soluble forms. Our data highlight a novel and universal paradigm whereby the complement innate immune system is using two synergistic strategies with the recognition of altered self-NA and missing self-CD46 signals to instruct and tailor the efficient removal of apoptotic and necrotic cells in immunoprivileged sites.

Mediators of innate immune recognition of bacteria concentrate in lipid rafts and facilitate lipopolysaccharide-induced cell activation

2002 ◽  
Vol 115 (12) ◽  
pp. 2603-2611 ◽  
Author(s):  
Martha Triantafilou ◽  
Kensuke Miyake ◽  
Douglas T. Golenbock ◽  
Kathy Triantafilou
Keyword(s):  
Lipid Rafts ◽  
Lipid Raft ◽  
Cell Activation ◽  
Imaging Techniques ◽  
Recognition System ◽  
Innate Immune ◽  
Membrane Microdomains ◽  
Immune Recognition ◽  
Cellular Activation ◽  
Signalling Molecules

The plasma membrane of cells is composed of lateral heterogeneities,patches and microdomains. These membrane microdomains or lipid rafts are enriched in glycosphingolipids and cholesterol and have been implicated in cellular processes such as membrane sorting and signal transduction. In this study we investigated the importance of lipid raft formation in the innate immune recognition of bacteria using biochemical and fluorescence imaging techniques. We found that receptor molecules that are implicated in lipopolysaccharide (LPS)-cellular activation, such as CD14, heat shock protein(hsp) 70, 90, Chemokine receptor 4 (CXCR4), growth differentiation factor 5(GDF5) and Toll-like receptor 4 (TLR4), are present in microdomains following LPS stimulation. Lipid raft integrity is essential for LPS-cellular activation, since raft-disrupting drugs, such as nystatin or MCD, inhibit LPS-induced TNF-α secretion. Our results suggest that the entire bacterial recognition system is based around the ligation of CD14 by bacterial components and the recruitment of multiple signalling molecules, such as hsp70, hsp90, CXCR4, GDF5 and TLR4, at the site of CD14-LPS ligation, within the lipid rafts.

scholarly journals Inhibition of Toll-like Receptor and Cytokine Signaling—A Unifying Theme in Ischemic Tolerance

2004 ◽  
Vol 24 (11) ◽  
pp. 1288-1304 ◽  
Author(s):  
Katalin Karikó ◽  
Drew Weissman ◽  
Frank A. Welsh
Keyword(s):  
Immune System ◽  
Inflammatory Response ◽  
Lipid Rafts ◽  
Inflammatory Cytokines ◽  
Innate Immune System ◽  
Endotoxin Tolerance ◽  
Ischemic Tolerance ◽  
Innate Immune ◽  
Cytokine Signaling ◽  
The Brain

Cerebral ischemia triggers acute inflammation, which exacerbates primary brain damage. Activation of the innate immune system is an important component of this inflammatory response. Inflammation occurs through the action of proinflammatory cytokines, such as TNF, IL-1β and IL-6, that alter blood flow and increase vascular permeability, thus leading to secondary ischemia and accumulation of immune cells in the brain. Production of these cytokines is initiated by signaling through Toll-like receptors (TLRs) that recognize host-derived molecules released from injured tissues and cells. Recently, great strides have been made in understanding the regulation of the innate immune system, particularly the signaling mechanisms of TLRs. Negative feedback inhibitors of TLRs and inflammatory cytokines have now been identified and characterized. It is also evident that lipid rafts exist in membranes and play a role in receptor-mediated inflammatory signaling events. In the present review, using this newly available large body of knowledge, we take a fresh look at studies of ischemic tolerance. Based on this analysis, we recognize a striking similarity between ischemic tolerance and endotoxin tolerance, an immune suppressive state characterized by hyporesponsiveness to lipopolysaccharide (LPS). In view of this analogy, and considering recent discoveries related to molecular mechanisms of endotoxin tolerance, we postulate that inhibition of TLR and proinflammatory cytokine signaling contributes critically to ischemic tolerance in the brain and other organs. Ischemic tolerance is a protective mechanism induced by a variety of preconditioning stimuli. Tolerance can be established with two temporal profiles: (i) a rapid form in which the trigger induces tolerance to ischemia within minutes and (ii) a delayed form in which development of protection takes several hours or days and requires de-novo protein synthesis. The rapid form of tolerance is achieved by direct interference with membrane fluidity, causing disruption of lipid rafts leading to inhibition of TLR/cytokine signaling pathways. In the delayed form of tolerance, the preconditioning stimulus first triggers the TLR/cytokine inflammatory pathways, leading not only to inflammation but also to simultaneous upregulation of feedback inhibitors of inflammation. These inhibitors, which include signaling inhibitors, decoy receptors, and anti-inflammatory cytokines, reduce the inflammatory response to a subsequent episode of ischemia. This novel interpretation of the molecular mechanism of ischemic tolerance highlights new avenues for future investigation into the prevention and treatment of stroke and related diseases.

scholarly journals Innate Pathways of Immune Activation in Transplantation

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Todd V. Brennan ◽  
Keri E. Lunsford ◽  
Paul C. Kuo
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Critical Role ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Microbial Pathogens ◽  
Immune Recognition ◽  
First Line ◽  
Adaptive Immune

Studies of the immune mechanisms of allograft rejection have predominantly focused on the adaptive immune system that includes T cells and B cells. Recent investigations into the innate immune system, which recognizes foreign antigens through more evolutionarily primitive pathways, have demonstrated a critical role of the innate immune system in the regulation of the adaptive immune system. Innate immunity has been extensively studied in its role as the host's first-line defense against microbial pathogens; however, it is becoming increasingly recognized for its ability to also recognize host-derived molecules that result from tissue damage. The capacity of endogenous damage signals acting through the innate immune system to lower immune thresholds and promote immune recognition and rejection of transplant grafts is only beginning to be appreciated. An improved understanding of these pathways may reveal novel therapeutic targets to decrease graft alloreactivity and increase graft longevity.

scholarly journals Prokaryotic ribosomal RNA stimulates zebrafish embryonic innate immune system

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Abhishikta Basu ◽  
Maki Yoshihama ◽  
Tamayo Uechi ◽  
Naoya Kenmochi
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
18S Rrna Gene ◽  
Positive Control ◽  
Innate Immune ◽  
Rrna Gene ◽  
Immune Recognition ◽  
E Coli

Abstract Objectives Cell-culture studies reported that prokaryotic RNA molecules among the various microbe-associated molecular patterns (MAMPs) were uniquely present in live bacteria and were categorized as viability-associated MAMPs. They also reported that specific nucleotide modifications are instrumental in the discrimination between self and nonself RNAs. The aim of this study was to characterize the in vivo immune induction potential of prokaryotic and eukaryotic ribosomal RNAs (rRNAs) using zebrafish embryos as novel whole animal model system. Additionally, we aimed to test the possible role of rRNA modifications in immune recognition. Results We used three immune markers to evaluate the induction potential of prokaryotic rRNA derived from Escherichia coli and eukaryotic rRNAs from chicken (nonself) and zebrafish (self). Lipopolysaccharide (LPS) of Pseudomonas aeruginosa served as a positive control. E. coli rRNA had an induction potential equivalent to that of LPS. The zebrafish innate immune system could discriminate between self and nonself rRNAs. Between the nonself rRNAs, E. coli rRNA was more immunogenic than chicken rRNA. The in vitro transcript of zebrafish 18S rRNA gene without the nucleotide modifications was not recognized by its own immune system. Our data suggested that prokaryotic rRNA is immunostimulatory in vivo and could be useful as an adjuvant.

scholarly journals Replication of Influenza A Virus in Secondary Lymphatic Tissue Contributes to Innate Immune Activation

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 622
Author(s):  
Sarah-Kim Friedrich ◽  
Rosa Schmitz ◽  
Michael Bergerhausen ◽  
Judith Lang ◽  
Vikas Duhan ◽  
...  
Keyword(s):  
Immune System ◽  
Influenza A Virus ◽  
Immune Activation ◽  
Influenza A ◽  
Lymphoid Organs ◽  
Innate Immune ◽  
Intravenous Route ◽  
Lymphatic Tissue ◽  
Innate Immune Activation ◽  
Secondary Lymphoid Organs

The replication of viruses in secondary lymphoid organs guarantees sufficient amounts of pattern-recognition receptor ligands and antigens to activate the innate and adaptive immune system. Viruses with broad cell tropism usually replicate in lymphoid organs; however, whether a virus with a narrow tropism relies on replication in the secondary lymphoid organs to activate the immune system remains not well studied. In this study, we used the artificial intravenous route of infection to determine whether Influenza A virus (IAV) replication can occur in secondary lymphatic organs (SLO) and whether such replication correlates with innate immune activation. Indeed, we found that IAV replicates in secondary lymphatic tissue. IAV replication was dependent on the expression of Sialic acid residues in antigen-presenting cells and on the expression of the interferon-inhibitor UBP43 (Usp18). The replication of IAV correlated with innate immune activation, resulting in IAV eradication. The genetic deletion of Usp18 curbed IAV replication and limited innate immune activation. In conclusion, we found that IAV replicates in SLO, a mechanism which allows innate immune activation.

Bacterial glycans and their interactions with lectins in the innate immune system

2019 ◽  
Vol 47 (6) ◽  
pp. 1569-1579 ◽  
Author(s):  
Mariano Prado Acosta ◽  
Bernd Lepenies
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Immune Responses ◽  
Innate Immune System ◽  
Bacterial Infections ◽  
Innate Immune ◽  
Immune Recognition ◽  
Lectin Receptors ◽  
Bacterial Surfaces ◽  
Bacterial Glycosylation

Bacterial surfaces are rich in glycoconjugates that are mainly present in their outer layers and are of great importance for their interaction with the host innate immune system. The innate immune system is the first barrier against infection and recognizes pathogens via conserved pattern recognition receptors (PRRs). Lectins expressed by innate immune cells represent an important class of PRRs characterized by their ability to recognize carbohydrates. Among lectins in innate immunity, there are three major classes including the galectins, siglecs, and C-type lectin receptors. These lectins may contribute to initial recognition of bacterial glycans, thus providing an early defence mechanism against bacterial infections, but they may also be exploited by bacteria to escape immune responses. In this review, we will first exemplify bacterial glycosylation systems; we will then describe modes of recognition of bacterial glycans by lectins in innate immunity and, finally, we will briefly highlight how bacteria have found ways to exploit these interactions to evade immune recognition.

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