Cytotoxicity of, and innate immune response to, size-controlled polypyrrole nanoparticles in mammalian cells

Biomaterials ◽  
2011 ◽  
Vol 32 (9) ◽  
pp. 2342-2350 ◽  
Author(s):  
Sojin Kim ◽  
Wan-Kyu Oh ◽  
Yoon Seon Jeong ◽  
Jin-Yong Hong ◽  
Bo-Ram Cho ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Mammalian Cells ◽  
Innate Immune ◽  
Polypyrrole Nanoparticles ◽  
Size Controlled

scholarly journals The transcription factors TFEB and TFE3 link the FLCN-AMPK signaling axis to innate immune response and pathogen resistance

2018 ◽  
Author(s):  
Leeanna El-Houjeiri ◽  
Elite Possik ◽  
Tarika Vijayaraghavan ◽  
Mathieu Paquette ◽  
José A Martina ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Mammalian Cells ◽  
Pathogen Resistance ◽  
Innate Immune ◽  
Negative Regulator ◽  
Energy Status ◽  
Rapid Reduction ◽  
Coupling Energy ◽  
Mtorc1 Signaling

AbstractTFEB and TFE3 are transcriptional regulators of the innate immune response, but the mechanisms regulating their activation upon pathogen infection are poorly elucidated. UsingC. elegansand mammalian models, we report that the master metabolic modulator 5’-AMP-activated protein kinase (AMPK) and its negative regulator Folliculin (FLCN) act upstream of TFEB/TFE3 in the innate immune response, independently of the mTORC1 signaling pathway. In nematodes, loss of FLCN or overexpression of AMPK conferred pathogen resistanceviaactivation of TFEB/TFE3-dependent antimicrobial genes, while ablation of total AMPK activity abolished this phenotype. Similarly, in mammalian cells, loss of FLCN or pharmacological activation of AMPK induced TFEB/TFE3-dependent pro-inflammatory cytokine expression. Importantly, a rapid reduction in cellular ATP levels in murine macrophages was observed upon lipopolysaccharide (LPS) treatment accompanied by an acute AMPK activation and TFEB nuclear localization. These results uncover an ancient, highly conserved and pharmacologically actionable mechanism coupling energy status with innate immunity.

Role of miRNA-146a in the regulation of the innate immune response and cancer

2008 ◽  
Vol 36 (6) ◽  
pp. 1211-1215 ◽  
Author(s):  
Andrew E. Williams ◽  
Mark M. Perry ◽  
Sterghios A. Moschos ◽  
Hanna M. Larner-Svensson ◽  
Mark A. Lindsay
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Mammalian Cells ◽  
Mrna Translation ◽  
Nuclear Factor Κb ◽  
Causal Link ◽  
Innate Immune ◽  
Major Function ◽  
Biological Responses

In mammalian cells, miRNAs (microRNAs) are the most abundant family of small non-coding RNAs that regulate mRNA translation through the RNA interference pathway. In general, it appears that the major function of miRNAs is in development, differentiation and homoeostasis, which is indicated by studies showing aberrant miRNA expression during the development of cancer. Interestingly, changes in the expression of miR-146a have been implicated in both the development of multiple cancers and in the negative regulation of inflammation induced via the innate immune response. Furthermore, miR-146a expression is driven by the transcription factor NF-κB (nuclear factor κB), which has been implicated as an important causal link between inflammation and carcinogenesis. In the present article, we review the evidence for a role of miR-146a in innate immunity and cancer and assess whether changes in miR-146a might link these two biological responses.

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.

scholarly journals Deficiency in Translesion DNA Polymerase ζ Induces an Innate Immune Response

2020 ◽  
Author(s):  
Sara K. Martin ◽  
Junya Tomida ◽  
Richard D. Wood
Keyword(s):  
Immune Response ◽  
Dna Polymerase ◽  
Innate Immune Response ◽  
Mammalian Cells ◽  
Dna Lesions ◽  
Innate Immune ◽  
Protective Function ◽  
Interferon Stimulated Genes ◽  
Protein Levels ◽  
Genomic Stress

ABSTRACTDNA polymerase pol ζ is regarded as a specialized DNA polymerase for bypass of DNA lesions. In mammalian cells, pol ζ also contributes to genomic stability during normal DNA replication. Disruption of Rev3l (the catalytic subunit of pol ζ) is toxic to cells and mice, with increased constitutive chromosome damage, including micronuclei. As the cellular manifestations of this genomic stress have remained unexplored, we measured genome-wide transcriptional changes by RNA-seq in pol ζ-defective cells. Expression of 1117 transcripts was altered by 4-fold or more in Rev3l knockout mouse embryonic fibroblasts (MEFs), with a pattern showing an induction of an innate immune response. We validated the increased expression of known interferon-stimulated genes (ISG) at the mRNA and protein levels. We found that the cGAS-STING axis, which senses cytosolic DNA, drives ISG expression in Rev3l knockout MEFs. These results reveal a new genome protective function of pol ζ and indicate that inhibition of pol ζ may be therapeutically useful by simultaneously increasing sensitivity to genotoxins and inducing a cytotoxic innate immune response.

scholarly journals Transcriptome Profiling of the Virus-Induced Innate Immune Response in Pteropus vampyrus and Its Attenuation by Nipah Virus Interferon Antagonist Functions

2015 ◽  
Vol 89 (15) ◽  
pp. 7550-7566 ◽  
Author(s):  
Nicole B. Glennon ◽  
Omar Jabado ◽  
Michael K. Lo ◽  
Megan L. Shaw
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Mammalian Cells ◽  
Nipah Virus ◽  
A549 Cells ◽  
Hendra Virus ◽  
Innate Immune ◽  
Viral Control ◽  
Content Type ◽  
Pteropus Vampyrus

ABSTRACTBats are important reservoirs for several viruses, many of which cause lethal infections in humans but have reduced pathogenicity in bats. As the innate immune response is critical for controlling viruses, the nature of this response in bats and how it may differ from that in other mammals are of great interest. Using next-generation transcriptome sequencing (mRNA-seq), we profiled the transcriptional response ofPteropus vampyrusbat kidney (PVK) cells to Newcastle disease virus (NDV), an avian paramyxovirus known to elicit a strong innate immune response in mammalian cells. ThePteropusgenus is a known reservoir of Nipah virus (NiV) and Hendra virus (HeV). Analysis of the 200 to 300 regulated genes showed that genes for interferon (IFN) and antiviral pathways are highly upregulated in NDV-infected PVK cells, including genes for beta IFN, RIG-I, MDA5, ISG15, and IRF1. NDV-infected cells also upregulated several genes not previously characterized to be antiviral, such as RND1, SERTAD1, CHAC1, and MORC3. In fact, we show that MORC3 is induced by both IFN and NDV infection in PVK cells but is not induced by either stimulus in human A549 cells. In contrast to NDV infection, HeV and NiV infection of PVK cells failed to induce these innate immune response genes. Likewise, an attenuated response was observed in PVK cells infected with recombinant NDVs expressing the NiV IFN antagonist proteins V and W. This study provides the first global profile of a robust virus-induced innate immune response in bats and indicates that henipavirus IFN antagonist mechanisms are likely active in bat cells.IMPORTANCEBats are the reservoir host for many highly pathogenic human viruses, including henipaviruses, lyssaviruses, severe acute respiratory syndrome coronavirus, and filoviruses, and many other viruses have also been isolated from bats. Viral infections are reportedly asymptomatic or heavily attenuated in bat populations. Despite their ecological importance to viral maintenance, research into their immune system and mechanisms for viral control has only recently begun. Nipah virus and Hendra virus are two paramyxoviruses associated with high mortality rates in humans and whose reservoir is thePteropusgenus of bats. Greater knowledge of the innate immune response ofP. vampyrusbats to viral infection may elucidate how bats serve as a reservoir for so many viruses.

scholarly journals West Nile Virus Nonstructural Protein 1 Inhibits TLR3 Signal Transduction

2008 ◽  
Vol 82 (17) ◽  
pp. 8262-8271 ◽  
Author(s):  
Jason R. Wilson ◽  
Paola Florez de Sessions ◽  
Megan A. Leon ◽  
Frank Scholle
Keyword(s):  
Signal Transduction ◽  
Immune Response ◽  
West Nile Virus ◽  
Innate Immune Response ◽  
Mammalian Cells ◽  
Innate Immune ◽  
Productive Infection ◽  
West Nile ◽  
Antiviral State ◽  
Nonstructural Protein 1

ABSTRACT The innate immune response is the first line of defense against foreign pathogens. The recognition of virus-associated molecular patterns, including double- and single-stranded RNA, by pattern recognition receptors initiates a cascade of signaling reactions. These result in the transcriptional upregulation and secretion of proinflammatory cytokines that induce an antiviral state. Many viruses have evolved mechanisms to antagonize these responses in order to help them establish a productive infection. We have previously shown that West Nile virus (WNV) is able to inhibit Toll-like receptor 3 (TLR3)-mediated activation of interferon (IFN) regulatory factor 3 (IRF3) (F. Scholle and P. W. Mason, Virology 342:77-87, 2005). In the present study, the WNV nonstructural (NS) proteins were analyzed individually for their ability to antagonize signal transduction mediated by TLR3. We report that expression of WNV NS1 inhibits TLR3-induced transcriptional activation of the IFN-β promoter and of an NF-κB-responsive promoter. This inhibition was due to a failure of the TLR3 ligand poly(I:C) to induce nuclear translocation of IRF3 and NF-κB. Furthermore, NS1 expression also inhibited TLR3-dependent production of interleukin-6 and the establishment of an antiviral state. The function of NS1 in flavivirus infection is not well understood. NS1 is required for viral RNA replication and is also secreted from mammalian cells but not from insect cells. Here, we identify a previously unrecognized role for NS1 in the modulation of signaling pathways of the innate immune response to WNV infection.

scholarly journals Hypothesis: Ran GTPase-Based Potential Therapeutic Interventions Against Lethal Microbial Infections

2002 ◽  
Vol 2 ◽  
pp. 684-689 ◽  
Author(s):  
Peter M.C. Wong
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Mammalian Cells ◽  
Immune Modulation ◽  
Therapeutic Potential ◽  
Cell Types ◽  
Innate Immune ◽  
Therapeutic Interventions ◽  
Surface Receptors ◽  
Host Innate Immune Response

Host innate immune response represents a vital immediate defense against infections by a diverse group of microorganisms that include bacteria, viruses, and fungi. Many types of cell surface receptors in mammalian cells specifically recognize particular groups of microorganisms and transmit response signals to the nuclei via multiple signal transduction pathways. These signaling pathways must merge at some point and are likely to be redundant, as the host innate immune response to many microorganisms is remarkably similar; it is characterized by the production of proinflammatory cytokines such as TNFα, IL-1, and IL-6 by the principal cell types – macrophages and dendritic cells. Since these cytokines influence greatly the magnitude of the cascade of inflammatory events, the proportion and the actual amount of each among the cytokine group may be a characteristic of each type of infections. Immune modulation by systematically up-regulate or down-modulate these cytokines would conceivably have major therapeutic potential. We have recently shown that two alleles of Ran cDNAs – RanT/n and RanC/d – may possess these characteristics. Thus the applica-tion of Ran to the treatment of septic shock, lethal anthrax shock, or adenovirus-induced toxicities may open up many interesting possibilities in the future.

scholarly journals Oral streptococci subvert the host innate immune response through hydrogen peroxide

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Yi Ling Tang ◽  
Tiow Suan Sim ◽  
Kai Soo Tan
Keyword(s):  
Hydrogen Peroxide ◽  
Immune Response ◽  
Innate Immune Response ◽  
Mammalian Cells ◽  
Innate Immune ◽  
Related Factor ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Oral Streptococci ◽  
Periodontal Health

AbstractIn periodontal health, oral streptococci constitute up to 80% of the plaque biofilm. Yet, destructive inflammatory events of the periodontium are rare. This observation suggests that oral streptococci may possess mechanisms to co-exist with the host. However, the mechanisms employed by oral streptococci to modulate the innate immune response have not been well studied. One of the key virulence factors produced by oral streptococci is hydrogen peroxide (H2O2). In mammalian cells, H2O2 triggers the activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key pathway mediating antioxidant defence. This study aimed to determine (1) if H2O2 producing oral streptococci activated the Nrf2 pathway in macrophages, and (2) if the activation of Nrf2 influenced the innate immune response. We found that oral streptococci downregulated the innate immune response in a H2O2 dependent manner through the activation of the Nrf2. The activation of the Nrf2 signalling pathway led to the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NFĸB), the key transcription factor regulating pro-inflammatory response. This study showed for the first time that oral streptococci are unlikely passive bystanders but could play an active role in the maintenance of periodontal health by preventing overt inflammation.

scholarly journals Chemical genetics and proteome-wide site mapping reveal cysteine MARylation by PARP-7 on immune-relevant protein targets

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Kelsie M Rodriguez ◽  
Sara C Buch-Larsen ◽  
Ilsa T Kirby ◽  
Ivan Rodriguez Siordia ◽  
David Hutin ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Mammalian Cells ◽  
Rna Binding ◽  
Chemical Genetics ◽  
Innate Immune ◽  
Site Preference ◽  
Protein Targets ◽  
Adp Ribosylation ◽  
Site Mapping

Poly(ADP-ribose) polymerase 7 (PARP-7) has emerged as a critically important member of a large enzyme family that catalyzes ADP-ribosylation in mammalian cells. PARP-7 is a critical regulator of the innate immune response. What remains unclear is the mechanism by which PARP-7 regulates this process, namely because the protein targets of PARP-7 mono-ADP-ribosylation (MARylation) are largely unknown. Here, we combine chemical genetics, proximity labeling, and proteome-wide amino acid ADP-ribosylation site profiling for identifying the direct targets and sites of PARP-7-mediated MARylation in a cellular context. We found that the inactive PARP family member, PARP-13—a critical regulator of the antiviral innate immune response—is a major target of PARP-7. PARP-13 is preferentially MARylated on cysteine residues in its RNA binding zinc finger domain. Proteome-wide ADP-ribosylation analysis reveals cysteine as a major MARylation acceptor of PARP-7. This study provides insight into PARP-7 targeting and MARylation site preference.

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