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https://www.readbyqxmd.com/read/28934563/hemophagocytic-lymphohistiocytosis
#1
Hanny Al-Samkari, Nancy Berliner
Hemophagocytic lymphohistiocytosis is a life-threatening disorder characterized by unbridled activation of cytotoxic T lymphocytes, natural killer (NK) cells, and macrophages resulting in hypercytokinemia and immunemediated injury of multiple organ systems. It is seen in both children and adults and is recognized as primary (driven by underlying genetic mutations that abolish critical proteins required for normal function of cytotoxic T cells and NK cells) or secondary (resulting from a malignant, infectious, or autoimmune stimulus without an identifiable underlying genetic trigger)...
September 13, 2017: Annual Review of Pathology
https://www.readbyqxmd.com/read/28934479/targeted-reconstruction-of-t-cell-receptor-sequence-from-single-cell-rna-seq-links-cdr3-length-to-t-cell-differentiation-state
#2
Shaked Afik, Kathleen B Yates, Kevin Bi, Samuel Darko, Jernej Godec, Ulrike Gerdemann, Leo Swadling, Daniel C Douek, Paul Klenerman, Eleanor J Barnes, Arlene H Sharpe, W Nicholas Haining, Nir Yosef
The T cell compartment must contain diversity in both T cell receptor (TCR) repertoire and cell state to provide effective immunity against pathogens. However, it remains unclear how differences in the TCR contribute to heterogeneity in T cell state. Single cell RNA-sequencing (scRNA-seq) can allow simultaneous measurement of TCR sequence and global transcriptional profile from single cells. However, current methods for TCR inference from scRNA-seq are limited in their sensitivity and require long sequencing reads, thus increasing the cost and decreasing the number of cells that can be feasibly analyzed...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934453/an-adjuvanted-a-h5n1-subvirion-vaccine-elicits-virus-specific-antibody-response-and-improves-protection-against-lethal-influenza-viral-challenge-in-mouse-model-of-protein-energy-malnutrition
#3
Enitra N Jones, Samuel Amoah, Weiping Cao, Suryaprakash Sambhara, Shivaprakash Gangappa
Background: Protein energy malnutrition (PEM) increases susceptibility to infectious diseases, including influenza infection, but no studies have addressed the potential influences of PEM on the immunogenicity and protective efficacy of avian influenza A(H5N1) vaccine. Methods: We investigated the role of PEM on vaccine-mediated protection after a lethal challenge with recombinant A(H5N1) virus using isocaloric diets providing either adequate protein (AP; 18% protein) or very low protein (VLP; 2% protein) in an established murine model of influenza vaccination...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934428/hiv-infected-children-have-elevated-levels-of-pd-1-memory-cd4-t-cells-with-low-proliferative-capacity-and-high-inflammatory-cytokine-effector-functions
#4
Julia Foldi, Lina Kozhaya, Bret McCarty, Mussa Mwamzuka, Fatma Marshed, Tiina Ilmet, Max Kilberg, Adam Kravietz, Aabid Ahmed, William Borkowsky, Derya Unutmaz, Alka Khaitan
Background: During human immunodeficiency virus (HIV) disease, chronic immune activation leads to T-cell exhaustion. PD-1 identifies "exhausted" CD8 T cells with impaired HIV-specific effector functions, but its role on CD4 T cells and in HIV-infected children is poorly understood. Methods: In a Kenyan cohort of vertically HIV-infected children, we measured PD-1+ CD4 T-cell frequencies and phenotype by flow cytometry and their correlation with HIV disease progression and immune activation...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934427/immunologic-profiling-of-human-metapneumovirus-for-the-development-of-targeted-immunotherapy
#5
Ifigeneia Tzannou, Sarah K Nicholas, Premal Lulla, Paibel I Aguayo-Hiraldo, Anisha Misra, Caridad A Martinez, Annette A Machado, Jordan S Orange, Pedro A Piedra, Juan F Vera, Ann M Leen
Human metapneumovirus (hMPV) is a respiratory virus detected in ≥9% of allogeneic hematopoietic stem cell transplant (HSCT) recipients, in whom it can cause significant morbidity and mortality. Given the lack of effective antivirals, we investigated the potential for immunotherapeutic intervention, using adoptively transferred T cells. Thus, we characterized the cellular immune response to the virus and identified F, N, M2-1, M, and P as immunodominant target antigens. Reactive T cells were polyclonal (ie, they expressed CD4 and CD8), T-helper type 1 polarized, and polyfunctional (ie, they produced interferon γ, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, and granzyme B), and they were able to kill autologous antigen-loaded targets...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934426/enhanced-macrophage-m1-polarization-and-resistance-to-apoptosis-enable-resistance-to-plague
#6
Emilia Pachulec, Rym Ben Abdelwahed Bagga, Lucie Chevallier, Hope O'Donnell, Chloé Guillas, Jean Jaubert, Xavier Montagutelli, Elisabeth Carniel, Christian E Demeure
Background: Susceptibility to infection is in part genetically driven, and C57BL/6 mice resist various pathogens through the proinflammatory response of their M1 macrophages (MPs). However, they are susceptible to plague. It has been reported elsewhere that Mus spretus SEG mice resist plague and develop an immune response characterized by a strong recruitment of MPs. Methods: The responses of C57BL/6 and SEG MPs exposed to Yersinia pestis in vitro were examined...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934369/in-vivo-activation-of-latent-hiv-with-a-synthetic-bryostatin-analog-effects-both-latent-cell-kick-and-kill-in-strategy-for-virus-eradication
#7
Matthew D Marsden, Brian A Loy, Xiaomeng Wu, Christina M Ramirez, Adam J Schrier, Danielle Murray, Akira Shimizu, Steven M Ryckbosch, Katherine E Near, Tae-Wook Chun, Paul A Wender, Jerome A Zack
The ability of HIV to establish a long-lived latent infection within resting CD4+ T cells leads to persistence and episodic resupply of the virus in patients treated with antiretroviral therapy (ART), thereby preventing eradication of the disease. Protein kinase C (PKC) modulators such as bryostatin 1 can activate these latently infected cells, potentially leading to their elimination by virus-mediated cytopathic effects, the host's immune response and/or therapeutic strategies targeting cells actively expressing virus...
September 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28934360/pkacs-attenuate-innate-antiviral-response-by-phosphorylating-visa-and-priming-it-for-march5-mediated-degradation
#8
Bing-Ru Yan, Lu Zhou, Ming-Ming Hu, Mi Li, Heng Lin, Yan Yang, Yan-Yi Wang, Hong-Bing Shu
Sensing of viral RNA by RIG-I-like receptors initiates innate antiviral response, which is mediated by the central adaptor VISA. How the RIG-I-VISA-mediated antiviral response is terminated at the late phase of infection is enigmatic. Here we identified the protein kinase A catalytic (PKAC) subunits α and β as negative regulators of RNA virus-triggered signaling in a redundant manner. Viral infection up-regulated cellular cAMP levels and activated PKACs, which then phosphorylated VISA at T54. This phosphorylation abrogated virus-induced aggregation of VISA and primed it for K48-linked polyubiquitination and degradation by the E3 ligase MARCH5, leading to attenuation of virus-triggered induction of downstream antiviral genes...
September 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28934357/from-bacterial-killing-to-immune-modulation-recent-insights-into-the-functions-of-lysozyme
#9
REVIEW
Stephanie A Ragland, Alison K Criss
Lysozyme is a cornerstone of innate immunity. The canonical mechanism for bacterial killing by lysozyme occurs through the hydrolysis of cell wall peptidoglycan (PG). Conventional type (c-type) lysozymes are also highly cationic and can kill certain bacteria independently of PG hydrolytic activity. Reflecting the ongoing arms race between host and invading microorganisms, both gram-positive and gram-negative bacteria have evolved mechanisms to thwart killing by lysozyme. In addition to its direct antimicrobial role, more recent evidence has shown that lysozyme modulates the host immune response to infection...
September 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28934318/identification-of-lag3-high-affinity-aptamers-by-ht-selex-and-conserved-motif-accumulation-cma
#10
Mario Martínez Soldevilla, Sandra Hervas, Helena Villanueva, Teresa Lozano, Obdulia Rabal, Julen Oyarzabal, Juan José Lasarte, Maurizio Bendandi, Susana Inoges, Ascensión López-Díaz de Cerio, Fernando Pastor
LAG3 receptor belongs to a family of immune-checkpoints expressed in T lymphocytes and other cells of the immune system. It plays an important role as a rheostat of the immune response. Focus on this receptor as a potential therapeutic target in cancer immunotherapy has been underscored after the success of other immune-checkpoint blockade strategies in clinical trials. LAG3 showcases the interest in the field of autoimmunity as several studies show that LAG3-targeting antibodies can also be used for the treatment of autoimmune diseases...
2017: PloS One
https://www.readbyqxmd.com/read/28934246/discovery-of-pf-06928215-as-a-high-affinity-inhibitor-of-cgas-enabled-by-a-novel-fluorescence-polarization-assay
#11
Justin Hall, Amy Brault, Fabien Vincent, Shawn Weng, Hong Wang, Darren Dumlao, Ann Aulabaugh, Dikran Aivazian, Dana Castro, Ming Chen, Jeffrey Culp, Ken Dower, Joseph Gardner, Steven Hawrylik, Douglas Golenbock, David Hepworth, Mark Horn, Lyn Jones, Peter Jones, Eicke Latz, Jing Li, Lih-Ling Lin, Wen Lin, David Lin, Frank Lovering, Nootaree Niljanskul, Ryan Nistler, Betsy Pierce, Olga Plotnikova, Daniel Schmitt, Suman Shanker, James Smith, William Snyder, Timothy Subashi, John Trujillo, Edyta Tyminski, Guoxing Wang, Jimson Wong, Bruce Lefker, Leslie Dakin, Karen Leach
Cyclic GMP-AMP synthase (cGAS) initiates the innate immune system in response to cytosolic dsDNA. After binding and activation from dsDNA, cGAS uses ATP and GTP to synthesize 2', 3' -cGAMP (cGAMP), a cyclic dinucleotide second messenger with mixed 2'-5' and 3'-5' phosphodiester bonds. Inappropriate stimulation of cGAS has been implicated in autoimmune disease such as systemic lupus erythematosus, thus inhibition of cGAS may be of therapeutic benefit in some diseases; however, the size and polarity of the cGAS active site makes it a challenging target for the development of conventional substrate-competitive inhibitors...
2017: PloS One
https://www.readbyqxmd.com/read/28934245/angiopoietin-like-protein-2-regulates-porphyromonas-gingivalis-lipopolysaccharide-induced-inflammatory-response-in-human-gingival-epithelial-cells
#12
Tasuku Ohno, Genta Yamamoto, Jun-Ichiro Hayashi, Eisaku Nishida, Hisashi Goto, Yasuyuki Sasaki, Takeshi Kikuchi, Mitsuo Fukuda, Yoshiaki Hasegawa, Makio Mogi, Akio Mitani
Angiopoietin-like protein 2 (ANGPTL2) maintains tissue homeostasis by inducing inflammation and angiogenesis. It is produced in infiltrating immune cells or resident cells, such as adipocytes, vascular endothelial cells, and tumor cells. We hypothesized that ANGPTL2 might play an important role as a unique mediator in both systemic and periodontal disease. We demonstrated an increased ANGPTL2 concentration in gingival crevicular fluid from chronic periodontitis patients. Porphyromonas gingivalis lipopolysaccharide (LPS) treatment strongly induced ANGPTL2 mRNA and protein levels in Ca9-22 human gingival epithelial cells...
2017: PloS One
https://www.readbyqxmd.com/read/28934217/elevated-humoral-response-to-cytomegalovirus-in-hiv-infected-individuals-with-poor-cd4-t-cell-immune-recovery
#13
Elisabet Gómez-Mora, Marta Massanella, Elisabet García, David Giles, Marta Bernadó, Victor Urrea, Jorge Carrillo, Dan Ouchi, Jordi Puig, Eugenia Negredo, Bonaventura Clotet, Julià Blanco, Cecilia Cabrera
Some HIV-infected c-ART-suppressed individuals show incomplete CD4+ T-cell recovery, abnormal T-cell activation and higher mortality. One potential source of immune activation could be coinfection with cytomegalovirus (CMV). IgG and IgM levels, immune activation, inflammation and T-cell death in c-ART-suppressed individuals with CD4+ T-cell counts >350 cells/μL (immunoconcordant, n = 133) or <350 cells/μL (immunodiscordant, n = 95) were analyzed to evaluate the effect of CMV humoral response on immune recovery...
2017: PloS One
https://www.readbyqxmd.com/read/28934210/oncolytic-potency-and-reduced-virus-tumor-specificity-in-oncolytic-virotherapy-a-mathematical-modelling-approach
#14
Khaphetsi Joseph Mahasa, Amina Eladdadi, Lisette de Pillis, Rachid Ouifki
In the present paper, we address by means of mathematical modeling the following main question: How can oncolytic virus infection of some normal cells in the vicinity of tumor cells enhance oncolytic virotherapy? We formulate a mathematical model describing the interactions between the oncolytic virus, the tumor cells, the normal cells, and the antitumoral and antiviral immune responses. The model consists of a system of delay differential equations with one (discrete) delay. We derive the model's basic reproductive number within tumor and normal cell populations and use their ratio as a metric for virus tumor-specificity...
2017: PloS One
https://www.readbyqxmd.com/read/28934167/live-attenuated-influenza-vaccine-contains-substantial-and-unexpected-amounts-of-defective-viral-genomic-rna
#15
Philip S Gould, Andrew J Easton, Nigel J Dimmock
The live attenuated influenza vaccine FluMist(®) was withdrawn in the USA by the Centers for Disease Control and Prevention after its failure to provide adequate protective immunity during 2013-2016. The vaccine uses attenuated core type A and type B viruses, reconfigured each year to express the two major surface antigens of the currently circulating viruses. Here Fluenz™ Tetra, the European version of this vaccine, was examined directly for defective-interfering (DI) viral RNAs. DI RNAs are deleted versions of the infectious virus genome, and have powerful biological properties including attenuation of infection, reduction of infectious virus yield, and stimulation of some immune responses...
September 21, 2017: Viruses
https://www.readbyqxmd.com/read/28934137/evidence-for-involvement-of-il-9-and-il-22-in-cows-milk-allergy-in-infants
#16
Karina V Barros, Vera L Flor Silveira, Marisa S Laranjeira, Neusa F Wandalsen, Susana Passeti, Roberta de Oliveira, Regina V Munekata, Paul S Noakes, Elizabeth A Miles, Philip C Calder
Although allergic inflammation is characterized by a T helper (Th) 2-dominant immune response, the discovery of a role for new T cell subsets in inflammatory diseases has added an additional layer of complexity to the understanding of the pathogeneses of allergic diseases. We evaluated plasma cytokine profiles in infants with cows' milk allergy (CMA), who were being treated with an elimination diet. In a prospective, randomized and controlled study, infants (aged 8.4 ± 3.9 months) with CMA were treated with an elimination diet for 120 days, which replaced cows' milk with a hydrolysed soy protein formula (n = 26) or a free amino acid formula (n = 20)...
September 21, 2017: Nutrients
https://www.readbyqxmd.com/read/28934122/invasion-of-dendritic-cells-macrophages-and-neutrophils-by-the-bordetella-adenylate-cyclase-toxin-a-subversive-move-to-fool-host-immunity
#17
REVIEW
Giorgio Fedele, Ilaria Schiavoni, Irena Adkins, Nela Klimova, Peter Sebo
Adenylate cyclase toxin (CyaA) is released in the course of B. pertussis infection in the host's respiratory tract in order to suppress its early innate and subsequent adaptive immune defense. CD11b-expressing dendritic cells (DC), macrophages and neutrophils are professional phagocytes and key players of the innate immune system that provide a first line of defense against invading pathogens. Recent findings revealed the capacity of B. pertussis CyaA to intoxicate DC with high concentrations of 3',5'-cyclic adenosine monophosphate (cAMP), which ultimately skews the host immune response towards the expansion of Th17 cells and regulatory T cells...
September 21, 2017: Toxins
https://www.readbyqxmd.com/read/28934110/a-recombinant-measles-vaccine-with-enhanced-resistance-to-passive-immunity
#18
Emily Julik, Jorge Reyes-Del Valle
Current measles vaccines suffer from poor effectiveness in young infants due primarily to the inhibitory effect of residual maternal immunity on vaccine responses. The development of a measles vaccine that resists such passive immunity would strongly contribute to the stalled effort toward measles eradication. In this concise communication, we show that a measles virus (MV) with enhanced hemagglutinin (H) expression and incorporation, termed MVvac2-H2, retained its enhanced immunogenicity, previously established in older mice, when administered to very young, genetically modified, MV-susceptible mice in the presence of passive anti-measles immunity...
September 21, 2017: Viruses
https://www.readbyqxmd.com/read/28934066/characterization-of-t-cell-immune-responses-in-clinical-trials-of-the-candidate-rts-s-malaria-vaccine
#19
Philippe Moris, Erik Jongert, Robbert G van der Most
The candidate malaria vaccine RTS,S has demonstrated 45.7% efficacy over 18 months against all clinical disease in a phase-III field study of African children. RTS,S targets the circumsporozoite protein (CSP), which is expressed on the Plasmodium sporozoite during the pre-erythrocyte stage of its life-cycle; the stage between mosquito bite and liver infection. Early in the development of RTS,S, it was recognized that CSP-specific cell-mediated immunity (CMI) was required to complement CSP-specific antibody-mediated immunity...
September 21, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28933967/aid-biology-a-pathological-and-clinical-perspective
#20
Meenal Choudhary, Anubhav Tamrakar, Amit Kumar Singh, Monika Jain, Ankit Jaiswal, Prashant Kodgire
Activation-induced cytidine deaminase (AID), primarily expressed in activated mature B lymphocytes in germinal centers, is the key factor in adaptive immune response against foreign antigens. AID is responsible for producing high-affinity and high-specificity antibodies against an infectious agent, through the physiological DNA alteration processes of antibody genes by somatic hypermutation (SHM) and class-switch recombination (CSR) and functions by deaminating deoxycytidines (dC) to deoxyuridines (dU), thereby introducing point mutations and double-stranded chromosomal breaks (DSBs)...
September 21, 2017: International Reviews of Immunology
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