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Articles 1 - 10 of 10
Full-Text Articles in Life Sciences
Role Of The Dna Sensor Sting In Protection From Lethal Infection Following Corneal And Intracerebral Challenge With Herpes Simplex Virus 1, Zachary M. Parker, Aisling A. Murphy, David. A. Leib
Role Of The Dna Sensor Sting In Protection From Lethal Infection Following Corneal And Intracerebral Challenge With Herpes Simplex Virus 1, Zachary M. Parker, Aisling A. Murphy, David. A. Leib
Dartmouth Scholarship
STING is a protein in the cytosolic DNA and cyclic dinucleotide sensor pathway that is critical for the initiation of innate responses to infection by various pathogens. Consistent with this, herpes simplex virus 1 (HSV-1) causes invariable and rapid lethality in STING-deficient (STING(-/-)) mice following intravenous (i.v.) infection. In this study, using real-time bioluminescence imaging and virological assays, as expected, we demonstrated that STING(-/-) mice support greater replication and spread in ocular tissues and the nervous system. In contrast, they did not succumb to challenge via the corneal route even with high titers of a virus that was routinely lethal …
Machine Learning Methods Enable Predictive Modeling Of Antibody Feature:Function Relationships In Rv144 Vaccinees, Ickwon Choi, Amy W. Chung, Todd J. Suscovich, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapha, Jaranit Kaewkungwal, Robert J. O'Connell, Donald Francis, Merlin L. Robb, Nelson L. Michael, Jerome H. Kim, Galit Alter, Margaret E. Ackerman, Chris Bailey-Kellogg
Machine Learning Methods Enable Predictive Modeling Of Antibody Feature:Function Relationships In Rv144 Vaccinees, Ickwon Choi, Amy W. Chung, Todd J. Suscovich, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapha, Jaranit Kaewkungwal, Robert J. O'Connell, Donald Francis, Merlin L. Robb, Nelson L. Michael, Jerome H. Kim, Galit Alter, Margaret E. Ackerman, Chris Bailey-Kellogg
Dartmouth Scholarship
The adaptive immune response to vaccination or infection can lead to the production of specific antibodies to neutralize the pathogen or recruit innate immune effector cells for help. The non-neutralizing role of antibodies in stimulating effector cell responses may have been a key mechanism of the protection observed in the RV144 HIV vaccine trial. In an extensive investigation of a rich set of data collected from RV144 vaccine recipients, we here employ machine learning methods to identify and model associations between antibody features (IgG subclass and antigen specificity) and effector function activities (antibody dependent cellular phagocytosis, cellular cytotoxicity, and cytokine …
Bioengineered Lysozyme Reduces Bacterial Burden And Inflammation In A Murine Model Of Mucoid Pseudomonas Aeruginosa Lung Infection, Charlotte C. Teneback, Thomas C. Scanlon, Matthew J. Wargo, Jenna L. Bement, Karl E. Griswold, Laurie W. Leclair
Bioengineered Lysozyme Reduces Bacterial Burden And Inflammation In A Murine Model Of Mucoid Pseudomonas Aeruginosa Lung Infection, Charlotte C. Teneback, Thomas C. Scanlon, Matthew J. Wargo, Jenna L. Bement, Karl E. Griswold, Laurie W. Leclair
Dartmouth Scholarship
The spread of drug-resistant bacterial pathogens is a growing global concern and has prompted an effort to explore potential adjuvant and alternative therapies derived from nature's repertoire of bactericidal proteins and peptides. In humans, the airway surface liquid layer is a rich source of antibiotics, and lysozyme represents one of the most abundant and effective antimicrobial components of airway secretions. Human lysozyme is active against both Gram-positive and Gram-negative bacteria, ac
Enhanced Phagocytic Activity Of Hiv-Specific Antibodies Correlates With Natural Production Of Immunoglobulins With Skewed Affinity For Fcγr2a And Fcγr2b, Margaret E. Ackerman, Anne-Sophie Dugast, Elizabeth G. Mcandrew, Stephen Tsoukas
Enhanced Phagocytic Activity Of Hiv-Specific Antibodies Correlates With Natural Production Of Immunoglobulins With Skewed Affinity For Fcγr2a And Fcγr2b, Margaret E. Ackerman, Anne-Sophie Dugast, Elizabeth G. Mcandrew, Stephen Tsoukas
Dartmouth Scholarship
While development of an HIV vaccine that can induce neutralizing antibodies remains a priority, decades of research have proven that this is a daunting task. However, accumulating evidence suggests that antibodies with the capacity to harness innate immunity may provide some protection. While significant research has focused on the cytolytic properties of antibodies in acquisition and control, less is known about the role of additional effector functions. In this study, we investigated antibody-dependent phagocytosis of HIV immune complexes, and we observed significant differences in the ability of antibodies from infected subjects to mediate this critical effector function. We observed both …
Adenosine Deaminase Enhances The Immunogenicity Of Human Dendritic Cells From Healthy And Hiv-Infected Individuals, Víctor Casanova, Isaac Isaac Naval-Macabuhay, Marta Massanella, Marta Rodríguez-García
Adenosine Deaminase Enhances The Immunogenicity Of Human Dendritic Cells From Healthy And Hiv-Infected Individuals, Víctor Casanova, Isaac Isaac Naval-Macabuhay, Marta Massanella, Marta Rodríguez-García
Dartmouth Scholarship
ADA is an enzyme implicated in purine metabolism, and is critical to ensure normal immune function. Its congenital deficit leads to severe combined immunodeficiency (SCID). ADA binding to adenosine receptors on dendritic cell surface enables T-cell costimulation through CD26 crosslinking, which enhances T-cell activation and proliferation. Despite a large body of work on the actions of the ecto-enzyme ADA on T-cell activation, questions arise on whether ADA can also modulate dendritic cell maturation. To this end we investigated the effects of ADA on human monocyte derived dendritic cell biology. Our results show that both the enzymatic and non-enzymatic activities of …
Functional Genomics Reveals An Essential And Specific Role For Stat1 In Protection Of The Central Nervous System Following Herpes Simplex Virus Corneal Infection, Tracy J. Pasieka, Cristian Cilloniz, Victoria S. Carter, Pamela Rosato, Michael G. Katze, David A. Leib
Functional Genomics Reveals An Essential And Specific Role For Stat1 In Protection Of The Central Nervous System Following Herpes Simplex Virus Corneal Infection, Tracy J. Pasieka, Cristian Cilloniz, Victoria S. Carter, Pamela Rosato, Michael G. Katze, David A. Leib
Dartmouth Scholarship
Innate immune deficiencies result in a spectrum of severe clinical outcomes following infection. In particular, there is a strong association between loss of the signal transducer and activator of transcription (Stat) pathway, breach of the blood-brain barrier (BBB), and virus-induced neuropathology. The gene signatures that characterize resistance, disease, and mortality in the virus-infected nervous system have not been defined. Herpes simplex virus type 1 (HSV-1) is commonly associated with encephalitis in humans, and humans and mice lacking Stat1 display increased susceptibility to HSV central nervous system (CNS) infections. In this study, two HSV-1 strains were used, KOS (wild type [WT]), …
Toxoplasma Gondii Rhoptry Kinase Rop16 Activates Stat3 And Stat6 Resulting In Cytokine Inhibition And Arginase-1-Dependent Growth Control, Barbara A. Butcher, Barbara A. Fox, Leah M. Rommereim, Sung Guk Kim, Kirk J. Maurer, Felix Yarovinsky, De'broski R. Herbert, David J. Bzik, Eric Y. Denkers
Toxoplasma Gondii Rhoptry Kinase Rop16 Activates Stat3 And Stat6 Resulting In Cytokine Inhibition And Arginase-1-Dependent Growth Control, Barbara A. Butcher, Barbara A. Fox, Leah M. Rommereim, Sung Guk Kim, Kirk J. Maurer, Felix Yarovinsky, De'broski R. Herbert, David J. Bzik, Eric Y. Denkers
Dartmouth Scholarship
The ROP16 kinase of Toxoplasma gondii is injected into the host cell cytosol where it activates signal transducer and activator of transcription (STAT)-3 and STAT6. Here, we generated a ROP16 deletion mutant on a Type I parasite strain background, as well as a control complementation mutant with restored ROP16 expression. We investigated the biological role of the ROP16 molecule during T. gondii infection. Infection of mouse bone marrow-derived macrophages with rop16-deleted (ΔROP16) parasites resulted in increased amounts of IL-12p40 production relative to the ROP16-positive RH parental strain. High level IL-12p40 production in ΔROP16 infection was dependent on the host …
Impaired Memory Cd8 T-Cell Responses Against An Immunodominant Retroviral Cryptic Epitope, Melanie R. Rutkowski, Cynthia A. Stevens, William R. Green
Impaired Memory Cd8 T-Cell Responses Against An Immunodominant Retroviral Cryptic Epitope, Melanie R. Rutkowski, Cynthia A. Stevens, William R. Green
Dartmouth Scholarship
The immunodominant cryptic epitope SYNTGRFPPL, encoded within open reading frame 2 of the LP-BM5 retroviral gag gene, is critical for protection against retroviral-induced pathogenesis. The goal of this study was to dissect the memory response against this unique immunodominant cryptic epitope. Unlike the protective acute effector population of SYNTGRFPPL-specific CD8 T cells, long-lived SYNTGRFPPL-specific CD8 T cells lacked the ability to protect susceptible mice infected with LP-BM5 retrovirus. Compared to memory CD8 T cells against a conventional epitope with similar MHC-I specificity, primed and restimulated using similar conditions, long-lived SYNTGRFPPL-specific CD8 T cells were impaired in their ability to recall …
Il-28 Supplants Requirement For Treg Cells In Protein Σ1-Mediated Protection Against Murine Experimental Autoimmune Encephalomyelitis (Eae), Agnieszka Rynda, Massimo Maddaloni, Javier Ochoa-Repáraz, Gayle Callis, David W. Pascual
Il-28 Supplants Requirement For Treg Cells In Protein Σ1-Mediated Protection Against Murine Experimental Autoimmune Encephalomyelitis (Eae), Agnieszka Rynda, Massimo Maddaloni, Javier Ochoa-Repáraz, Gayle Callis, David W. Pascual
Dartmouth Scholarship
Conventional methods to induce tolerance in humans have met with limited success. Hence, efforts to redirect tolerogen uptake using reovirus adhesin, protein sigma 1 (pσ1), may circumvent these shortcomings based upon the recent finding that when reovirus pσ1 is engineered to deliver chicken ovalbumin (OVA) mucosally, tolerance is obtained, even with a single dose. To test whether single-dose tolerance can be induced to treat EAE, proteolipid protein (PLP130–151) was genetically fused to OVA to pσ1 (PLP:OVA-pσ1) and shown to significantly ameliorate EAE, suppressing proinflammatory cytokines by IL-10+ forkhead box P3 (FoxP3)+ CD25+CD4+ T …
Mucosal Immunity In Toxoplasma Gondii Infection, J. Schulthess, D. Fourreau, S. Darche, B. Meresse, L. Kasper, N. Cerf-Bensussan, D. Buzoni-Gatel
Mucosal Immunity In Toxoplasma Gondii Infection, J. Schulthess, D. Fourreau, S. Darche, B. Meresse, L. Kasper, N. Cerf-Bensussan, D. Buzoni-Gatel
Dartmouth Scholarship
Toxoplasma gondii is an intracellular parasite that frequently infects a large spectrum of warm-blooded animals. This parasite induces abortion and establishes both chronic and silent infections, particularly in the brain. Parasite penetration into the host activates a strong anti-parasite immune response. In the present paper, we will discuss the interplay between innate and adaptive immunity that occurs within the infected intestine to clear the parasite and to maintain intestinal homeostasis despite the exacerbation of an inflammatory immune response.