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https://www.readbyqxmd.com/read/29321276/ifn-regulatory-factor-3-balances-th1-and-t-follicular-helper-immunity-during-nonlethal-blood-stage-plasmodium-infection
#1
Kylie R James, Megan S F Soon, Ismail Sebina, Daniel Fernandez-Ruiz, Gayle Davey, Urijah N Liligeto, Arya Sheela Nair, Lily G Fogg, Chelsea L Edwards, Shannon E Best, Lianne I M Lansink, Kate Schroder, Jane A C Wilson, Rebecca Austin, Andreas Suhrbier, Steven W Lane, Geoffrey R Hill, Christian R Engwerda, William R Heath, Ashraful Haque
Differentiation of CD4+ Th cells is critical for immunity to malaria. Several innate immune signaling pathways have been implicated in the detection of blood-stage Plasmodium parasites, yet their influence over Th cell immunity remains unclear. In this study, we used Plasmodium-reactive TCR transgenic CD4+ T cells, termed PbTII cells, during nonlethal P. chabaudi chabaudi AS and P. yoelii 17XNL infection in mice, to examine Th cell development in vivo. We found no role for caspase1/11, stimulator of IFN genes, or mitochondrial antiviral-signaling protein, and only modest roles for MyD88 and TRIF-dependent signaling in controlling PbTII cell expansion...
January 10, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29317664/human-cytomegalovirus-encoded-us9-targets-mavs-and-sting-signaling-to-evade-type-i-interferon-immune-responses
#2
Hyun Jin Choi, Areum Park, Sujin Kang, Eunhye Lee, Taeyun A Lee, Eun A Ra, Jiseon Lee, Sungwook Lee, Boyoun Park
Human cytomegalovirus (HCMV) has evolved sophisticated immune evasion mechanisms that target both the innate and adaptive immune responses. However, how HCMV encoded proteins are involved in this immune escape is not clear. Here, we show that HCMV glycoprotein US9 inhibits the IFN-β response by targeting the mitochondrial antiviral-signaling protein (MAVS) and stimulator of interferon genes (STING)-mediated signaling pathways. US9 accumulation in mitochondria attenuates the mitochondrial membrane potential, leading to promotion of MAVS leakage from the mitochondria...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29311560/a-central-role-for-pi3k-akt-signaling-pathway-in-linking-samhd1-deficiency-to-the-type-i-interferon-signature
#3
Changhoon Oh, Jeongmin Ryoo, Kiwon Park, Baek Kim, Michele B Daly, DongYeon Cho, Kwangseog Ahn
The autoimmune disorder Aicardi-Goutières syndrome (AGS) is characterized by a constitutive type I interferon response. SAMHD1 possesses both dNTPase and RNase activities and mutations in SAMHD1 cause AGS; however, how SAMHD1-deficiency causes the type I interferon response in patients with AGS remains unknown. Here, we show that endogenous RNA substrates accumulated in the absence of SAMHD1 act as a major immunogenic source for the type I interferon response. Reconstitution of SAMHD1-negative human cells with wild-type but not RNase-defective SAMHD1 abolishes spontaneous type I interferon induction...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29297844/predominant-role-of-ips-1-over-trif-adaptor-proteins-in-early-innate-immune-response-against-zika-virus-in-mice
#4
Jocelyne Piret, Julie Carbonneau, Chantal Rhéaume, Mariana Baz, Guy Boivin
Toll-like receptors and RNA helicases are involved in the control of RNA virus infection through production of type I interferons (IFNs). To delineate the relative contributions of these signalling pathways in the innate immune response and the control of Zika virus (ZIKV) pathogenesis, the impact of a deficiency in TRIF and/or IPS-1 adaptor proteins was investigated in mice. Mice were infected intravenously with ZIKV and monitored for clinical signs for 14 days. Groups of mice were sacrificed on days 1, 3 and 7 post-infection (p...
January 3, 2018: Journal of General Virology
https://www.readbyqxmd.com/read/29249322/saponin-quil-a-up-regulates-type-i-interferon-regulated-gene-and-type-i-and-ii-interferon-expressions-which-are-suppressed-by-porcine-reproductive-and-respiratory-syndrome-virus
#5
Wasin Charerntantanakul, Dante Fabros
Porcine reproductive and respiratory syndrome virus (PRRSV) suppresses innate immune response following infection of myeloid antigen-presenting cells. Poor innate immune response results in weak and delayed PRRSV-specific adaptive immunity, and facilitates PRRSV replication, pathogenesis, and persistent infection. Numerous efforts have been made to enhance the effective innate and adaptive immune defenses to PRRSV, however, only a few attempts have so far elicited satisfactory results. The present study aims to evaluate in vitro the potential of saponin quil A to enhance the expression of type I interferon (IFN)-regulated gene, type I and II IFNs, and pro-inflammatory cytokines in PRRSV-inoculated peripheral blood mononuclear cells (PBMC)...
January 2018: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/29247853/cytosolic-sensing-of-immuno-stimulatory-dna-the-enemy-within
#6
REVIEW
Rekha Dhanwani, Mariko Takahashi, Sonia Sharma
In the cytoplasm, DNA is sensed as a universal danger signal by the innate immune system. Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor/enzyme that catalyzes formation of 2'-5'-cGAMP, an atypical cyclic di-nucleotide second messenger that binds and activates the Stimulator of Interferon Genes (STING), resulting in recruitment of Tank Binding Kinase 1 (TBK1), activation of the transcription factor Interferon Regulatory Factor 3 (IRF3), and trans-activation of innate immune response genes, including type I Interferon cytokines (IFN-I)...
December 13, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29246809/adaptive-evolution-of-interferon-regulatory-factors-is-not-correlated-with-body-scale-reduction-or-loss-in-schizothoracine-fish
#7
Delin Qi, Yan Chao, Jian Liang, Qiang Gao, Rongrong Wu, Ian Mather, Yongli Zhao, Qichang Chen
Body scales in teleost fish are the first line of defense in protecting the fish from invading pathogens. However, the relationship between the adaptive evolution of immune-related genes and changes in the body scale-covering of fish has not been previously studied. Schizothoracine fish, characterized by progressive reduction of body scales from the primitive to the highly specialized species, are a good group to investigate this relationship. We obtained 11 IRF genes (IRF1-11) from 14 of schizothoracine fish representing primitive, specialized, and highly specialized species, of which seven IRF genes (IRF2, IRF3, IRF5, IRF6, IRF7, IRF8 and IRF9) contained the complete CDS...
December 12, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29244871/inflammatory-monocytes-mediate-control-of-acute-alphavirus-infection-in-mice
#8
Kelsey C Haist, Kristina S Burrack, Bennett J Davenport, Thomas E Morrison
Chikungunya virus (CHIKV) and Ross River virus (RRV) are mosquito-transmitted alphaviruses that cause debilitating acute and chronic musculoskeletal disease. Monocytes are implicated in the pathogenesis of these infections; however, their specific roles are not well defined. To investigate the role of inflammatory Ly6ChiCCR2+ monocytes in alphavirus pathogenesis, we used CCR2-DTR transgenic mice, enabling depletion of these cells by administration of diptheria toxin (DT). DT-treated CCR2-DTR mice displayed more severe disease following CHIKV and RRV infection and had fewer Ly6Chi monocytes and NK cells in circulation and muscle tissue compared with DT-treated WT mice...
December 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29242168/akt1-distinctively-suppresses-myd88-depenedent-and-trif-dependent-toll-like-receptor-signaling-in-a-kinase-activity-independent-manner
#9
Kosuke Zenke, Masashi Muroi, Ken-Ichi Tanamoto
We found that AKT1, a primary effector molecule of PI3K-AKT signaling, distinctively suppressed Toll-like receptor (TLR)-mediated MyD88-dependent and Toll/IL-1R domain-containing adaptor inducing IFN-β (TRIF)-dependent signaling by inhibiting NF-κB activation and IRF3 activity independently of its kinase activity. In AKT1 knockout RAW264.7 cells, lipopolysaccharide (LPS)-induced transcription and protein production of cytokines including IL-1β and TNF-α (regulated by the MyD88-dependent pathway), as well as IFN-β and RANTES (C-C motif chemokine ligand 5: CCL-5; regulated by the TRIF-dependent pathways) was enhanced compared to wild type cells...
December 11, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29241042/the-adenovirus-e1a-c-terminus-suppresses-a-delayed-antiviral-response-and-modulates-ras-signaling
#10
Nathan R Zemke, Arnold J Berk
The N-terminal half of adenovirus e1a assembles multimeric complexes with host proteins that repress innate immune responses and force host cells into S-phase. In contrast, the functions of e1a's C-terminal interactions with FOXK, DCAF7, and CtBP are unknown. We found that these interactions modulate RAS signaling, and that a single e1a molecule must bind all three of these host proteins to suppress activation of a subset of IFN-stimulated genes (ISGs). These ISGs were otherwise induced in primary respiratory epithelial cells at 12 hr p...
December 13, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29241030/expression-profiles-of-genes-involved-in-tlrs-and-nlrs-signaling-pathways-of-water-buffaloes-infected-with-fasciola-gigantica
#11
Fu-Kai Zhang, Jun-Ling Hou, Ai-Jiang Guo, Ai-Ling Tian, Zhao-An Sheng, Wen-Bin Zheng, Wei-Yi Huang, Hany M Elsheikha, Xing-Quan Zhu
Infection of ruminants and humans with Fasciola gigantica is attracting increasing attention due to its economic impact and public health significance. However, little is known of innate immune responses during F. gigantica infection. Here, we investigated the expression profiles of genes involved in Toll-like receptors (TLRs) and NOD-like receptors (NLRs) signaling pathways in buffaloes infected with 500F. gigantica metacercariae. Serum, liver and peripheral blood mononuclear cell (PBMC) samples were collected from infected and control buffaloes at 3, 10, 28, and 70days post infection (dpi)...
December 11, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29229676/teleost-specific-tlr19-localizes-to-endosome-recognizes-dsrna-recruits-trif-triggers-both-ifn-and-nf-%C3%AE%C2%BAb-pathways-and-protects-cells-from-grass-carp-reovirus-infection
#12
Jianfei Ji, Youliang Rao, Quanyuan Wan, Zhiwei Liao, Jianguo Su
TLRs are pivotal pattern recognition receptors in initiating innate immunity and triggering adaptive immunity. TLR pathways have been comprehensively investigated in mammals. However, the teleost-specific TLR19 pathway remains largely unknown. In this study, we identified TLR19 from grass carp (Ctenopharyngodon idella), and explored the ligand, adaptor, and signaling pathways. Pathogen-associated molecular pattern binding and luciferase activity assays indicate that TLR19 recognizes and responds to dsRNA analog (polyinosinic:polycytidylic acid)...
December 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29222027/tbk1-from-orange-spotted-grouper-exerts-antiviral-activity-against-fish-viruses-and-regulates-interferon-response
#13
Yin Hu, Youhua Huang, Jiaxin Liu, Jingcheng Zhang, Qiwei Qin, Xiaohong Huang
TANK-binding kinase-1 (TBK1) has been well studied in mammals because of its importance in type I interferon induction in antiviral immunity. However, the roles of fish TBK1 in virus infection still remained largely uncertain. In the current study, a TBK1 homolog from orange-spotted grouper (Epinephelus coioides) (EcTBK1) was cloned and its roles in fish viral infections were investigated. Sequence analysis showed that EcTBK1 encoded a 723-amino acid peptide which shared 98% and 73% identity to large yellow croaker (Larimichthys crocea) and human (homo sapiens), respectively...
December 5, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29221127/long-noncoding-rnas-expression-profile-and-functional-networks-in-rheumatoid-arthritis
#14
Donghua Xu, Ye Jiang, Lu Yang, Xixing Hou, Jihong Wang, Weijun Gu, Xiaodong Wang, Lanyu Liu, Juan Zhang, Hongying Lu
The modifying effects of long noncoding RNAs (lncRNAs) in rheumatoid arthritis (RA) recently have drawn much attention; however, the underlying mechanisms remain largely unknown. Herein, we aim to investigate the expression profile of lncRNAs in RA and identify promising targets for RA diagnosis and treatment. Microarray screening and real-time PCR of lncRNAs were performed by use of serum samples from 3 RA patients and 3 healthy controls. Significantly differentially expressed lncRNAs were verified in serum samples from 43 RA patients and 40 healthy controls by real-time PCR...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29215015/malaria-parasite-dna-harbouring-vesicles-activate-cytosolic-immune-sensors
#15
Xavier Sisquella, Yifat Ofir-Birin, Matthew A Pimentel, Lesley Cheng, Paula Abou Karam, Natália G Sampaio, Jocelyn Sietsma Penington, Dympna Connolly, Tal Giladi, Benjamin J Scicluna, Robyn A Sharples, Andreea Waltmann, Dror Avni, Eli Schwartz, Louis Schofield, Ziv Porat, Diana S Hansen, Anthony T Papenfuss, Emily M Eriksson, Motti Gerlic, Andrew F Hill, Andrew G Bowie, Neta Regev-Rudzki
STING is an innate immune cytosolic adaptor for DNA sensors that engage malaria parasite (Plasmodium falciparum) or other pathogen DNA. As P. falciparum infects red blood cells and not leukocytes, how parasite DNA reaches such host cytosolic DNA sensors in immune cells is unclear. Here we show that malaria parasites inside red blood cells can engage host cytosolic innate immune cell receptors from a distance by secreting extracellular vesicles (EV) containing parasitic small RNA and genomic DNA. Upon internalization of DNA-harboring EVs by human monocytes, P...
December 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/29212905/cyclic-gmp-amp-synthase-is-the-cytosolic-sensor-of-plasmodium-falciparum-genomic-dna-and-activates-type-i-ifn-in-malaria
#16
Carolina Gallego-Marin, Jacob E Schrum, Warrison A Andrade, Scott A Shaffer, Lina F Giraldo, Alvaro M Lasso, Evelyn A Kurt-Jones, Kate A Fitzgerald, Douglas T Golenbock
Innate immune receptors have a key role in the sensing of malaria and initiating immune responses. As a consequence of infection, systemic inflammation emerges and is directly related to signs and symptoms during acute disease. We have previously reported that plasmodial DNA is the primary driver of systemic inflammation in malaria, both within the phagolysosome and in the cytosol of effector cells. In this article, we demonstrate that Plasmodium falciparum genomic DNA delivered to the cytosol of human monocytes binds and activates cyclic GMP-AMP synthase (cGAS)...
December 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29207132/irf3-signaling-pathway-serves-an-important-role-in-poly-i-c-induced-procollagen-reduction-in-human-skin-fibroblasts
#17
Cheng Yao, Sangbum Han, Chi-Hyun Park, Ye-Ji Kim, Dong Hun Lee, Jin Ho Chung
Pattern recognition receptors (PRRs) are part of the immune system. They can recognize pathogen‑associated molecular patterns (PAMPs). Toll‑like receptors (TLRs) and retinoic acid‑inducible gene 1 (RIG‑1)‑like receptors (RLRs) are 2 types of PRR in the innate immune system. Double‑stranded RNA (dsRNA) can exist as a PAMP, including dsRNA viruses. dsRNA is known as a ligand not only for TLR3 but also for RLRs, including melanoma differentiation‑associated gene 5 and RIG‑1. Collagen is the main structural protein in the extracellular space in the skin...
November 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29201911/transmissible-gastroenteritis-virus-papain-like-protease-1-antagonizes-production-of-interferon-%C3%AE-through-its-deubiquitinase-activity
#18
Xiaoliang Hu, Jin Tian, Hongtao Kang, Dongchun Guo, Jiasen Liu, Dafei Liu, Qian Jiang, Zhijie Li, Juanjuan Qu, Liandong Qu
Coronaviruses (CoVs), such as human coronavirus NL63 (HCoV-NL63), severe acute respiratory syndrome CoV (SARS-CoV), murine hepatitis virus (MHV), porcine epidemic diarrhea virus (PEDV), and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), encode papain-like (PL) proteases that inhibit Sendai virus- (SeV-) induced interferon (IFN-β) production. Recently, the crystal structure of transmissible gastroenteritis virus (TGEV) PL1 has been solved, which was similar to that of SARS-CoV PL2pro, which may antagonize host innate immunity...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29194722/the-rna-genome-of-hepatitis-e-virus-robustly-triggers-antiviral-interferon-response
#19
Wenshi Wang, Yijin Wang, Changbo Qu, Shan Wang, Jianhua Zhou, Wanlu Cao, Lei Xu, Buyun Ma, Mohamad S Hakim, Yuebang Yin, Tiancheng Li, Maikel P Peppelenbosch, Jingmin Zhao, Qiuwei Pan
The outcomes of hepatitis E virus (HEV) infection are diverse, ranging from asymptomatic carrier, self-limiting acute infection, fulminant hepatitis to persistent infection. This is closely associated with the immunological status of the host. This study aims to understand the innate cellular immunity as the first-line defense mechanisms in response to HEV infection. Phosphorylation of STAT1, a hallmark of the activation of antiviral interferon (IFN) response, was observed in the liver tissues of majority of HEV infected patients, but not in the liver of uninfected individuals...
December 1, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29181006/protective-effect-of-panax-notoginseng-root-water-extract-against-influenza-a-virus-infection-by-enhancing-antiviral-interferon-mediated-immune-responses-and-natural-killer-cell-activity
#20
Jang-Gi Choi, Young-Hee Jin, Heeeun Lee, Tae Woo Oh, Nam-Hui Yim, Won-Kyung Cho, Jin Yeul Ma
Influenza is an acute respiratory illness caused by the influenza A virus, which causes economic losses and social disruption mainly by increasing hospitalization and mortality rates among the elderly and people with chronic diseases. Influenza vaccines are the most effective means of preventing seasonal influenza, but can be completely ineffective if there is an antigenic mismatch between the seasonal vaccine virus and the virus circulating in the community. In addition, influenza viruses resistant to antiviral drugs are emerging worldwide...
2017: Frontiers in Immunology
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