scholarly journals Matrix protein CCN1 induced by bacterial DNA and CpG ODN limits lung inflammation and contributes to innate immune homeostasis

2014 ◽  
Vol 8 (2) ◽  
pp. 243-253 ◽  
Author(s):  
H-G Moon ◽  
Z Qin ◽  
T Quan ◽  
L Xie ◽  
C S Dela Cruz ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Matrix Protein ◽  
Innate Immune ◽  
Immune Homeostasis ◽  
Cpg Odn ◽  
Bacterial Dna

FOXO-dependent regulation of innate immune homeostasis

Nature ◽  
2010 ◽  
Vol 463 (7279) ◽  
pp. 369-373 ◽  
Author(s):  
Thomas Becker ◽  
Gerrit Loch ◽  
Marc Beyer ◽  
Ingo Zinke ◽  
Anna C. Aschenbrenner ◽  
...  
Keyword(s):  
Innate Immune ◽  
Immune Homeostasis

scholarly journals MAVS: A Two-Sided CARD Mediating Antiviral Innate Immune Signaling and Regulating Immune Homeostasis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yunqiang Chen ◽  
Yuheng Shi ◽  
Jing Wu ◽  
Nan Qi
Keyword(s):  
Signal Transduction ◽  
Innate Immune ◽  
Immune Homeostasis ◽  
Type I ◽  
Interferon Signaling ◽  
Immune Signaling ◽  
Post Translational Modifications ◽  
Innate Immune Signaling ◽  
Mitochondrial Antiviral Signaling ◽  
Mitochondrial Antiviral Signaling Protein

Mitochondrial antiviral signaling protein (MAVS) functions as a “switch” in the immune signal transduction against most RNA viruses. Upon viral infection, MAVS forms prion-like aggregates by receiving the cytosolic RNA sensor retinoic acid-inducible gene I-activated signaling and further activates/switches on the type I interferon signaling. While under resting state, MAVS is prevented from spontaneously aggregating to switch off the signal transduction and maintain immune homeostasis. Due to the dual role in antiviral signal transduction and immune homeostasis, MAVS has emerged as the central regulation target by both viruses and hosts. Recently, researchers show increasing interest in viral evasion strategies and immune homeostasis regulations targeting MAVS, especially focusing on the post-translational modifications of MAVS, such as ubiquitination and phosphorylation. This review summarizes the regulations of MAVS in antiviral innate immune signaling transduction and immune homeostasis maintenance.

scholarly journals Regulation of the Ebola Virus VP24 Protein by SUMO

2019 ◽  
Vol 94 (1) ◽  
Author(s):  
Santiago Vidal ◽  
Ahmed El Motiam ◽  
Rocío Seoane ◽  
Viktorija Preitakaite ◽  
Yanis Hichem Bouzaher ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Viral Protein ◽  
Matrix Protein ◽  
Ebola Virus ◽  
Nuclear Translocation ◽  
Critical Role ◽  
Innate Immune ◽  
Type I ◽  
Negative Modulator

ABSTRACT Some viruses take advantage of conjugation of ubiquitin or ubiquitin-like proteins to enhance their own replication. One example is Ebola virus, which has evolved strategies to utilize these modification pathways to regulate the viral proteins VP40 and VP35 and to counteract the host defenses. Here, we show a novel mechanism by which Ebola virus exploits the ubiquitin and SUMO pathways. Our data reveal that minor matrix protein VP24 of Ebola virus is a bona fide SUMO target. Analysis of a SUMOylation-defective VP24 mutant revealed a reduced ability to block the type I interferon (IFN) pathway and to inhibit IFN-mediated STAT1 nuclear translocation, exhibiting a weaker interaction with karyopherin 5 and significantly diminished stability. Using glutathione S-transferase (GST) pulldown assay, we found that VP24 also interacts with SUMO in a noncovalent manner through a SIM domain. Mutation of the SIM domain in VP24 resulted in a complete inability of the protein to downmodulate the IFN pathway and in the monoubiquitination of the protein. We identified SUMO deubiquitinating enzyme ubiquitin-specific-processing protease 7 (USP7) as an interactor and a negative modulator of VP24 ubiquitination. Finally, we show that mutation of one ubiquitination site in VP24 potentiates the IFN modulatory activity of the viral protein and its ability to block IFN-mediated STAT1 nuclear translocation, pointing to the ubiquitination of VP24 as a negative modulator of the VP24 activity. Altogether, these results indicate that SUMO interacts with VP24 and promotes its USP7-mediated deubiquitination, playing a key role in the interference with the innate immune response mediated by the viral protein. IMPORTANCE The Ebola virus VP24 protein plays a critical role in escape of the virus from the host innate immune response. Therefore, deciphering the molecular mechanisms modulating VP24 activity may be useful to identify potential targets amenable to therapeutics. Here, we identify the cellular proteins USP7, SUMO, and ubiquitin as novel interactors and regulators of VP24. These interactions may represent novel potential targets to design new antivirals with the ability to modulate Ebola virus replication.

scholarly journals Interferon Alpha Characterization and Its Comparative Expression in PBM Cells of Capra hircus and Antelope cervicapra Cultured in the Presence of TLR9 Agonist

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Ramesh Doreswamy ◽  
Mohini Saini ◽  
Devendra Swarup ◽  
Vivek Kumar Singh ◽  
Suchitra Upreti ◽  
...  
Keyword(s):  
Interferon Alpha ◽  
Amino Acid Level ◽  
Innate Immune ◽  
Type I Interferons ◽  
Capra Hircus ◽  
Total Leukocyte Count ◽  
Nucleotide Sequencing ◽  
Type I ◽  
Cpg Odn ◽  
Tlr9 Agonist

TLR9 plays pivotal role in innate immune responses through upregulation of costimulatory molecules and induction of proinflammatory cytokines like type I interferons including interferon alpha (IFNA). The present study characterized IFNA cDNA and predicted protein sequences in goat and black buck. Response of the PBM cells to TLR9 agonist CpG ODN C and Phorbol Myristate Acetate (PMA) was evaluated by realtime PCR. IFNA coding sequences were amplified from leukocyte cDNA and cloned in pGEMT-easy vector for nucleotide sequencing. Sequence analysis revealed 570 bp, IFNA ORF encoding 189 amino acids in goat and black buck. Black buck and goat IFNA has 92.1% to 94.7% and 93% to 95.6% similarity at nucleotide level, 86.3% to 89.5% and 70.9% to 91.6% identity at amino acid level with other ruminants, respectively. Nonsynonymous substitutions exceeding synonymous substitutions indicated IFNA evolved through positive selection among ruminants. In spite of lower total leukocyte count, the innate immune cells like monocytes and neutrophils were more in black buck compared to goat. In addition, CpG ODN C-stimulated PBM cells revealed raised IFNA transcript in black buck than goat. These findings indicate sturdy genetically governed immune system in wild antelope black buck compared to domestic ruminant goat.

scholarly journals Surfactant protein D and bronchopulmonary dysplasia: a new way to approach an old problem

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Raquel Arroyo ◽  
Paul S. Kingma
Keyword(s):  
Immune Response ◽  
Preterm Infants ◽  
Bronchopulmonary Dysplasia ◽  
Lung Tissue ◽  
Lung Inflammation ◽  
Tissue Injury ◽  
Surfactant Protein ◽  
Immune Defense ◽  
Innate Immune ◽  
Surfactant Protein D

AbstractSurfactant protein D (SP-D) is a collectin protein synthesized by alveolar type II cells in the lungs. SP-D participates in the innate immune defense of the lungs by helping to clear infectious pathogens and modulating the immune response. SP-D has shown an anti-inflammatory role by down-regulating the release of pro-inflammatory mediators in different signaling pathways such as the TLR4, decreasing the recruitment of inflammatory cells to the lung, and modulating the oxidative metabolism in the lungs. Recombinant human SP-D (rhSP-D) has been successfully produced mimicking the structure and functions of native SP-D. Several in vitro and in vivo experiments using different animal models have shown that treatment with rhSP-D reduces the lung inflammation originated by different insults, and that rhSP-D could be a potential treatment for bronchopulmonary dysplasia (BPD), a rare disease for which there is no effective therapy up to date. BPD is a complex disease in preterm infants whose incidence increases with decreasing gestational age at birth. Lung inflammation, which is caused by different prenatal and postnatal factors like infections, lung hyperoxia and mechanical ventilation, among others, is the key player in BPD. Exacerbated inflammation causes lung tissue injury that results in a deficient gas exchange in the lungs of preterm infants and frequently leads to long-term chronic lung dysfunction during childhood and adulthood. In addition, low SP-D levels and activity in the first days of life in preterm infants have been correlated with a worse pulmonary outcome in BPD. Thus, SP-D mediated functions in the innate immune response could be critical aspects of the pathogenesis in BPD and SP-D could inhibit lung tissue injury in this preterm population. Therefore, administration of rhSP-D has been proposed as promising therapy that could prevent BPD.

scholarly journals Upstream ORFs Prevent MAVS Spontaneous Aggregation and Regulate Innate Immune Homeostasis

iScience ◽  
2020 ◽  
Vol 23 (5) ◽  
pp. 101059 ◽  
Author(s):  
Yuheng Shi ◽  
Jing Wu ◽  
Tiansheng Zhong ◽  
Wenting Zhu ◽  
Guolan She ◽  
...  
Keyword(s):  
Innate Immune ◽  
Immune Homeostasis ◽  
Spontaneous Aggregation

scholarly journals Identification of a Retroelement-Containing Human Transcript Induced in the Nucleus by Vaccination

2019 ◽  
Vol 20 (12) ◽  
pp. 2875
Author(s):  
Tomoyuki Honda ◽  
Keiko Takemoto ◽  
Keiji Ueda
Keyword(s):  
Immune Activation ◽  
Promoter Activity ◽  
Mammalian Genome ◽  
Innate Immune ◽  
Endogenous Retroviruses ◽  
Immune Homeostasis ◽  
Biological Processes ◽  
Human Genomic ◽  
Lines Of Evidence

Endogenous retroelements constitute almost half of the mammalian genome. Given that more than 60% of human genomic bases are transcribed, transcripts containing these retroelements may impact various biological processes. However, the physiological roles of most retroelement-containing transcripts are yet to be revealed. Here, we profiled the expression of retroelement-containing human transcripts during vaccination and found that vaccination upregulated transcripts containing only particular retroelements, such as the MLT-int element of endogenous retroviruses. MLT-int-containing transcripts were distributed mainly in the nucleus, suggesting their unique roles in the nucleus. Furthermore, we demonstrated that MLT-int RNA suppressed interferon promoter activity in the absence of immune stimuli. Based on these lines of evidence, we speculate a model of a role of the previously unnoticed MLT-int element in preventing excess innate immune activation after elimination of immune stimuli. Our results may emphasize the importance of retroelement-containing transcripts in maintaining host immune homeostasis.

Sign in / Sign up

Export Citation Format

Share Document