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https://www.readbyqxmd.com/read/27926941/type-1-interferons-and-nk-cells-limit-murine-cytomegalovirus-escape-from-the-lymph-node-subcapsular-sinus
#1
Helen E Farrell, Kimberley Bruce, Clara Lawler, Rhonda D Cardin, Nicholas J Davis-Poynter, Philip G Stevenson
Cytomegaloviruses (CMVs) establish chronic, systemic infections. Peripheral infection spreads via lymph nodes, which are also a focus of host defence. Thus, this is a point at which systemic infection spread might be restricted. Subcapsular sinus macrophages (SSM) captured murine CMV (MCMV) from the afferent lymph and poorly supported its replication. Blocking the type I interferon (IFN-I) receptor (IFNAR) increased MCMV infection of SSM and of the fibroblastic reticular cells (FRC) lining the subcapsular sinus, and accelerated viral spread to the spleen...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926863/chronic-infection-depletes-hematopoietic-stem-cells-through-stress-induced-terminal-differentiation
#2
Katie A Matatall, Mira Jeong, Siyi Chen, Deqiang Sun, Fengju Chen, Qianxing Mo, Marek Kimmel, Katherine Y King
Chronic infections affect a third of the world's population and can cause bone marrow suppression, a severe condition that increases mortality from infection. To uncover the basis for infection-associated bone marrow suppression, we conducted repeated infection of WT mice with Mycobacterium avium. After 4-6 months, mice became pancytopenic. Their hematopoietic stem and progenitor cells (HSPCs) were severely depleted and displayed interferon gamma (IFN-γ) signaling-dependent defects in self-renewal. There was no evidence of increased HSPC mobilization or apoptosis...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926855/temporally-programmed-cd8%C3%AE-dc-activation-enhances-combination-cancer-immunotherapy
#3
Alice Tzeng, Monique J Kauke, Eric F Zhu, Kelly D Moynihan, Cary F Opel, Nicole J Yang, Naveen Mehta, Ryan L Kelly, Gregory L Szeto, Willem W Overwijk, Darrell J Irvine, K Dane Wittrup
Numerous synergistic cancer immunotherapy combinations have been identified, but the effects of relative dose timing are rarely considered. In established syngeneic mouse tumor models, we found that staggering interferon-α (IFNα) administration after, rather than before or simultaneously with, serum-persistent interleukin-2 (IL-2) and tumor-specific antibody significantly increased long-term survival. Successful combination therapy required IFNα-induced activation of cross-presenting CD8α(+) dendritic cells (DCs) following the release of antigenic tumor debris by the IL-2- and antibody-mediated immune response...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27925386/interferon-free-therapies-for-patients-with-chronic%C3%A2-hepatitis-c-genotype-3-infection-a-systematic-review
#4
Vicente Gimeno-Ballester, María Buti, Ramón San Miguel, Mar Riveiro, Rafael Esteban
INTRODUCTION: Treatment of hepatitis C virus (HCV) infection with genotype 3 remains a challenge. The HCV elimination rate with direct acting antivirals (DAAs) is lower than the values reported for other HCV genotypes. In addition, genotype 3 infected patients have a higher risk of disease progression and hepatocellular carcinoma. The aim of this study was to review the relevant literature concerning treatment of HCV genotype 3 patients with interferon-free regimens. MATERIAL AND METHODS: A literature search was conducted in the PubMed/Medline, Embase, and Web of Science electronic databases...
December 7, 2016: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/27925355/epigenetic-analysis-of-the-ifn%C3%AE-3-gene-identifies-a-novel-marker-for-response-to-therapy-in-hcv-infected-subjects
#5
Jeffrey F Waring, J Wade Davis, Emily Dumas, Daniel Cohen, Kenneth Idler, Stephen Abel, Robert Georgantas, Thomas Podsadecki, Sandeep Dutta
Chronic hepatitis C virus (HCV) infection is characterized by high inter-individual variability in response to pegylated interferon and ribavirin. A genetic polymorphism on chromosome 19 (rs12979860) upstream of interferon-λ-3 (IFNλ3) is associated with a 2-fold change in sustained virologic response rate after 48 weeks of treatment with pegylated interferon/ribavirin in HCV genotype 1 (GT1) treatment-naïve patients. We conducted epigenetic analysis on the IFNλ3 promoter to investigate whether DNA methylation is associated with response to HCV therapy...
December 7, 2016: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/27924822/il-21-dependent-expansion-of-memory-like-nk-cells-enhances-protective-immune-responses-against-mycobacterium-tuberculosis
#6
S Venkatasubramanian, S Cheekatla, P Paidipally, D Tripathi, E Welch, A R Tvinnereim, R Nurieva, R Vankayalapati
Natural killer (NK) cells are traditionally considered as innate cells, but recent studies suggest that NK cells can distinguish antigens, and that memory NK cells expand and protect against viral pathogens. Limited information is available about the mechanisms involved in memory-like NK cell expansion, and their role in bacterial infections and vaccine-induced protective immune responses. In the current study, using a mouse model of tuberculosis (TB) infection, we found that interferon-gamma producing CD3-NKp46+CD27+KLRG1+ memory-like NK cells develop during Bacille Calmette-Guérin vaccination, expand, and provide protection against challenge with Mycobacterium tuberculosis (M...
December 7, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27924780/activity-of-ergoferon-against-lethal-influenza-a-h3n2-virus-infection-in-mice
#7
Maria A Skarnovich, Alexandra G Emelyanova, Nataliia V Petrova, Alena A Borshcheva, Evgeniy A Gorbunov, Oleg Yu Mazurkov, Maksim O Skarnovich, Sergey A Tarasov, Larisa N Shishkina, Oleg I Epstein
BACKGROUND: The Influenza A virus accounts for serious annual viral upper respiratory tract infections. It is constantly able to modify its antigenic structure, thus evading host defence mechanisms. Moreover, currently available anti-influenza agents have a rather limited application, emphasising the further need for new effective treatments. One of them is Ergoferon, a drug, containing combined polyclonal antibodies - anti-interferon gamma, anti-CD4 receptor, and anti-histamine - in released-active form...
December 7, 2016: Antiviral Therapy
https://www.readbyqxmd.com/read/27923923/antiviral-innate-immune-response-interferes-with-the-formation-of-replication-associated-membrane-structures-induced-by-a-positive-strand-rna-virus
#8
Diede Oudshoorn, Barbara van der Hoeven, Ronald W A L Limpens, Corrine Beugeling, Eric J Snijder, Montserrat Bárcena, Marjolein Kikkert
: Infection with nidoviruses like corona- and arteriviruses induces a reticulovesicular network of interconnected endoplasmic reticulum (ER)-derived double-membrane vesicles (DMVs) and other membrane structures. This network is thought to accommodate the viral replication machinery and protect it from innate immune detection. We hypothesized that the innate immune response has tools to counteract the formation of these virus-induced replication organelles in order to inhibit virus replication...
December 6, 2016: MBio
https://www.readbyqxmd.com/read/27923871/serum-lipid-profile-changes-predict-neurodegeneration-in-interferon-b1a-treated-multiple-sclerosis-patients
#9
Tomas Uher, Kelly Fellows, Dana Horakova, Robert Zivadinov, Manuela Vaneckova, Lukas Sobisek, Michaela Tyblova, Zdenek Seidl, Jan Krasensky, Niels Bergsland, Bianca Weinstock-Guttman, Eva Havrdova, Murali Ramanathan
PURPOSE: To determine whether changes in cholesterol profiles after IFN-beta1a treatment initiation following the first demyelinating event suggestive of MS are associated with clinical and MRI outcomes over 4 years. METHODS: 131 patients (age: 27.9 +/- 7.8 years, 63% female) with serial 3-monthly clinical and 12-monthly MRI follow-up over 4 years were investigated. Serum cholesterol profiles including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were obtained at baseline, 1 month, 3 months, and every 6 months thereafter...
December 6, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27923823/bortezomib-relieves-immune-tolerance-in-nasopharyngeal-carcinoma-via-stat1-suppression-and-indoleamine-2-3-dioxygenase-downregulation
#10
Guan-Min Jiang, Jun Du, Wei-Feng Ma, Hui Wang, Yu Qiu, Qiu-Gui Zhang, Wei Xu, Hui-Fang Liu, Hong-Sheng Wang, Jian-Ping Liang
Radiotherapy is the primary treatment for nasopharyngeal carcinoma (NPC). Patients with intermediate and advanced stage NPC receiving only radiotherapy have limited survival, so newer immunotherapeutic approaches are sought. The major impediment to better clinical outcomes is tumor immune tolerance. Indoleamine 2, 3-dioxygenase (IDO), an interferon-γ (IFNγ)-inducible enzyme, is a major inducer of immune tolerance during tumor development; therefore, inhibition of the IDO pathway is an important modality for cancer treatment...
December 6, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27923600/determinants-of-orofacial-clefting-ii-effects-of-5-aza-2-deoxycytidine-on-gene-methylation-during-development-of-the-first-branchial-arch
#11
Ratnam S Seelan, Partha Mukhopadhyay, Dennis R Warner, Irina A Smolenkova, M Michele Pisano, Robert M Greene
Defects in development of the secondary palate, which arise from the embryonic first branchial arch (1-BA), can cause cleft palate (CP). Administration of 5-Aza-2'-deoxycytidine (AzaD), a demethylating agent, to pregnant mice on gestational day 9.5 resulted in complete penetrance of CP in fetuses. Several genes critical for normal palatogenesis were found to be upregulated in 1-BA, 12hours after AzaD exposure. MethylCap-Seq (MCS) analysis identified several differentially methylated regions (DMRs) in DNA extracted from AzaD-exposed 1-BAs...
December 3, 2016: Reproductive Toxicology
https://www.readbyqxmd.com/read/27923570/recombinant-dna-vaccine-of-hantavirus-gn-and-lamp1-induced-long-term-immune-protection-in-mice
#12
Dong-Bo Jiang, Li-Juan Sun, Lin-Feng Cheng, Jin-Peng Zhang, Shao-Bo Xiao, Yuan-Jie Sun, Shu-Ya Yang, Jing Wang, Fang-Lin Zhang, Kun Yang
BACKGROUND: Prophylaxis is widely adopted the best choice against Hemorrhagic fever with renal syndrome (HFRS) caused by Hantavirus. However, loss of memory immune response maintenance remains as major shortcoming in current HFRS vaccine. A recombinant DNA vaccine, pVAX-LAMP/Gn was previously proved efficient, requiring long-term evaluations. METHODS & RESULTS: Immune responses of Balb/c mice were assessed by specific and neutralizing antibodies, interferon-γ ELISpot assay, and cytotoxic T-lymphocyte cytotoxicity assay...
December 3, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27923408/pharmacokinetic-and-pharmacodynamic-characterization-of-a-novel-formulation-containing-co-formulated-interferons-alpha-2b-and-gamma-in-healthy-male-volunteers
#13
Idrian García-García, Ignacio Hernández-González, Alina Díaz-Machado, Carlos A González-Delgado, Sonia Pérez-Rodríguez, Yanelda García-Vega, Rosario Campos-Mojena, Ángela D Tuero-Iglesias, Carmen M Valenzuela-Silva, Alieski Cruz-Ramírez, Alis Martín-Trujillo, Héctor Santana-Milián, Pedro A López-Saura, Iraldo Bello-Rivero
BACKGROUND: More potent antitumor activity is desired in Interferon (IFN)-treated cancer patients. This could be achieved by combining IFN alpha and IFN gamma. The aim of this work was to characterize the pharmacokinetics and pharmacodynamics of a novel formulation containing a co-formulated combination of IFNs alpha-2b and gamma (CIGB-128-A). METHODS: A group of nine healthy male subjects received intramuscularly 24.5 × 10(6) IU of CIGB-128-A. IFN concentrations were evaluated for 48 h...
December 7, 2016: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27922937/repurposing-ospemifene-for-potentiating-an-antigen-specific-immune-response
#14
Chiao-Jung Kao, Gregory T Wurz, Yi-Chen Lin, Daniel P Vang, Brian Phong, Michael W DeGregorio
OBJECTIVE: Ospemifene, an estrogen receptor agonist/antagonist approved for the treatment of dyspareunia and vaginal dryness in postmenopausal women, has potential new indications as an immune modulator. The overall objective of the present series of preclinical studies was to evaluate the immunomodulatory activity of ospemifene in combination with a peptide cancer vaccine. METHODS: Immune regulating effects, mechanism of action and structure activity relationships of ospemifene and related compounds were evaluated by examining expression of T-cell activating cytokines in vitro, and antigen-specific immune response and cytotoxic T-lymphocyte activity in vivo...
December 5, 2016: Menopause: the Journal of the North American Menopause Society
https://www.readbyqxmd.com/read/27922679/repetitive-extragenic-palindromic-dna-sequences-from-brucella%C3%A2-melitensis-stimulate-toll-like-receptor-9-signaling-in-macrophages
#15
Hui Yu, Liyun Bai, Yaxian Zhang, Zhanli Wang, Yongchun Yu
Brucella DNA activates the host innate immune system via the intracellular Toll-like receptor 9 (TLR9). However, the Brucella DNA sequences which are responsible for these immunostimulatory effects remain to be elucidated. The present study demonstrated that repetitive extragenic palindromic (REPs) sequences present in Brucella DNA were able to stimulate macrophages through TLR9. The induction of interferon-α (IFN-α) production by Brucella REPs was detected in cultured RAW264.7 mouse macrophages as well as in Wistar rats...
December 6, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27922590/neutrophils-are-essential-in-short-hairpin-rna-of-indoleamine-2-3-dioxygenase-mediated-antitumor-efficiency
#16
Kuan-Ting Liu, Yao-Hua Liu, Hsin-Liang Liu, Inn-Wen Chong, Meng-Chi Yen, Po-Lin Kuo
Indoleamine 2,3-dioxygenase (IDO) is a rate limiting enzyme in tryptophan-degrading pathways and IDO activity results in immune suppression. Targeting IDO is a strategy of cancer immunotherapies. Our previous studies demonstrate that delivery of short hairpin against IDO (IDO shRNA) suppresses tumor growth and increases neutrophils infiltration into tumor. Neutrophils reveal antitumorigenic "N1" or protumorigenic "N2" phenotype in tumor microenvironment. However, the function of IDO shRNA-induced neutrophils is not clear...
December 6, 2016: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/27922126/viral-and-bacterial-co-infection-in-severe-pneumonia-triggers-innate-immune-responses-and-specifically-enhances-ip-10-a-translational-study
#17
Jonathan Hoffmann, Daniela Machado, Olivier Terrier, Stephane Pouzol, Mélina Messaoudi, Wilma Basualdo, Emilio E Espínola, Rosa M Guillen, Manuel Rosa-Calatrava, Valentina Picot, Thomas Bénet, Hubert Endtz, Graciela Russomando, Gláucia Paranhos-Baccalà
Mixed viral and bacterial infections are widely described in community-acquired pneumonia; however, the clinical implications of co-infection on the associated immunopathology remain poorly studied. In this study, microRNA, mRNA and cytokine/chemokine secretion profiling were investigated for human monocyte-derived macrophages infected in-vitro with Influenza virus A/H1N1 and/or Streptococcus pneumoniae. We observed that the in-vitro co-infection synergistically increased interferon-γ-induced protein-10 (CXCL10, IP-10) expression compared to the singly-infected cells conditions...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27921406/house-dust-mites-confer-a-distinct-immunological-feature-among-dermatitis
#18
Safa Baris, Ahmet Ozen, Tuba Akdeniz, Elif Karakoc-Aydiner, Ovgu Aydin, Hulya Ercan, Ismail Ogulur, Yildiz Camcioglu, Reha Cengizlier, Cuyan Demirkesen, Deniz Yucelten, Gulderen Demirel, Isil B Barlan
Atopic dermatitis (AD) is a heterogeneous disease with regard to clinical phenotype and natural history. We investigated T cell subtypes and cytokine responses in peripheral blood and skin lesions of AD patients with various sensitivities. Immunological studies were performed in 27 subjects: 9 house dust mite (HDM)-sensitized; 6 subjects with sensitizations other than HDM; 7 non-allergic AD patients and 5 healthy controls. Among those, skin biopsy samples of 13 subjects were evaluated for immunohistochemical analyses, as well...
August 2016: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/27921220/increased-cell-free-mitochondrial-dna-is-a-marker-of-ongoing-inflammation-and-better-neurocognitive-function-in-virologically-suppressed-hiv-infected-individuals
#19
Josué Pérez-Santiago, Michelli F De Oliveira, Susanna R Var, Tyler R C Day, Steven P Woods, Sara Gianella, Sanjay R Mehta
Cell-free mitochondrial DNA (mtDNA) is a highly immunogenic molecule that is associated with several inflammatory conditions and with neurocognitive impairment during untreated HIV infection. Here, we investigate how cell-free mtDNA in cerebrospinal fluid (CSF) is associated with inflammation, neuronal damage, and neurocognitive functioning in the context of long-term suppressive antiretroviral therapy (ART). We quantified the levels of cell-free mtDNA in the CSF from 41 HIV-infected individuals with completely suppressed HIV RNA levels in blood plasma (<50 copies/mL) by droplet digital PCR...
December 5, 2016: Journal of Neurovirology
https://www.readbyqxmd.com/read/27921059/duodenal-recurrence-of-fibrolamellar-carcinoma-12-years-after-partial-hepatectomy-and-adjuvant-chemotherapy
#20
Héctor Adrián Díaz Hernández, Ismael Antonio Gómez Ruiz, Aldo Torre
Fibrolamellar carcinoma (FLC) has a better prognosis than hepatocellular carcinoma; however, it is a highly recurrent disease. A 17-year-old woman presented with FLC with regional disease at the right lobe of the liver and underwent right hepatic lobe resection plus adjuvant chemotherapy with interferon α and adriamycin. She then presented at age 29 years with anemia. Endoscopy revealed an exofitic lesion in the duodenum, which was a recurrence of FLC. The patient underwent duodenal partial resection of a metastatic FLC tumor with disease-free edges and without neural or lymphoid-vascular involvement, a nonreported site of recurrence...
August 2016: ACG Case Reports Journal
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