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Investigating The Significance Of Acetylation By Hopz3 In Pseudomonas Syringae, George Walters-Marrah 2017 University of Central Florida

Investigating The Significance Of Acetylation By Hopz3 In Pseudomonas Syringae, George Walters-Marrah

George Walters-Marrah

Pseudomonas syringae (Psy) is a bacterial plant pathogen and the causative agent of leaf spot. Psy’s success is largely due to its type III secretion system (T3SS) that enables it to inject a large repertoire of effector proteins into plant cells. The effector protein HopZ3 has been shown to suppress immune responses and promote bacterial growth. HopZ3 can bind to and acetylate the effector protein AvrPto and the tomato protein Pto, a member of the Prf immune complex found in tomato. Pto recognizes and interacts with AvrPto to activate the immune response during infection, but HopZ3-mediated acetylation reduces AvrPto-Pto ...


Pathways Involved In Recognition And Induction Of Trained Innate Immunity By Plasmodium Falciparum, Jacob E. Schrum 2017 University of Massachusetts Medical School

Pathways Involved In Recognition And Induction Of Trained Innate Immunity By Plasmodium Falciparum, Jacob E. Schrum

GSBS Dissertations and Theses

Malarial infection in naïve individuals induces a robust innate immune response, but our understanding of the mechanisms by which the innate immune system recognizes malaria and regulates its response remain incomplete. Our group previously showed that stimulation of macrophages with Plasmodium falciparum genomic DNA (gDNA) and AT-rich oligodeoxynucleotides (ODNs) derived from this gDNA induces the production of type I interferons (IFN-I) through a STING/TBK1/IRF3-dependent pathway; however, the identity of the upstream cytosolic DNA receptor remained elusive. Here, we demonstrate that this IFN-I response is dependent on cyclic GMP-AMP synthase (cGAS). cGAS produced the cyclic dinucleotide 2’3’-cGAMP ...


Role Of Tim3 In Mediating T Cell Exhaustion During Chronic Mycobacterium Tuberculosis Infection, Miye K. Jacques 2017 University of Massachusetts Medical School

Role Of Tim3 In Mediating T Cell Exhaustion During Chronic Mycobacterium Tuberculosis Infection, Miye K. Jacques

GSBS Dissertations and Theses

Mycobacterium tuberculosis infection is one of the leading causes of mortality worldwide. One third of the population is estimated to be infected, however only 5-10% of those individuals can transmit the disease. While T cell immunity initially limits mycobacterium growth, it is unclear why T cell immunity fails to sterilize the infection and prevent subsequent recrudescence. One hypothesis is T cell exhaustion is mediating the failure of T cell immunity late during infection. Here we show the development of T cell exhaustion during chronic infection, and that the inhibitory receptor T cell-immunoglobulin and mucin domain containing 3 (TIM3) mediates the ...


Edaxadiene: A New Bioactive Diterpene From Mycobacterium Tuberculosis, Francis M. Mann, Meimei Xu, Xiaoming Chen, D. Bruce Fulton, David G. Russell, Reuben J. Peters 2017 Iowa State University

Edaxadiene: A New Bioactive Diterpene From Mycobacterium Tuberculosis, Francis M. Mann, Meimei Xu, Xiaoming Chen, D. Bruce Fulton, David G. Russell, Reuben J. Peters

Reuben J. Peters

Mycobacterium tuberculosis remains a widespread and devastating human pathogen. Presented here is the characterization of an atypical class I diterpene cyclase from M. tuberculosis that catalyzes an unusual cyclization reaction in converting the known M. tuberculosis metabolite halimadienyl diphosphate to a further cyclized novel diterpene, which we have termed edaxadiene, as it directly inhibits maturation of the phagosomal compartment in which the bacterium is taken up during infection.


Magnesium Depletion Triggers Production Of An Immune Modulating Diterpenoid In Mycobacterium Tuberculosis, Francis M. Mann, Brian C. VanderVen, Reuben J. Peters 2017 Iowa State University

Magnesium Depletion Triggers Production Of An Immune Modulating Diterpenoid In Mycobacterium Tuberculosis, Francis M. Mann, Brian C. Vanderven, Reuben J. Peters

Reuben J. Peters

Mycobacterium tuberculosis (Mtb) is the causative agent of the human disease Tuberculosis, and remains a worldwide health threat responsible for ~1.7 million deaths annually. During infection, Mtb prevents acidification of the engulfing phagosome, thus blocking endocytic progression and eventually leading to stable residence. The diterpenoid metabolite isotuberculosinol (isoTb) exhibits biological activity indicative of a role in this early arrest of phagosome maturation. Presumably, isoTb production should be induced by phagosomal entry. However, the relevant enzymatic genes are not transcriptionally upregulated during engulfment. Previous examination of the initial biosynthetic enzyme (Rv3377c/MtHPS) involved in isoTb biosynthesis revealed striking inhibition by ...


Central Role Of Il-23 And Il-17 Producing Eosinophils As Immunomodulatory Effector Cells In Acute Pulmonary Aspergillosis And Allergic Asthma, Evelyn V. Santos Guerra, Chrono K. Lee, Charles A. Specht, Bhawna Yadav, Haibin Huang, Ali Akalin, Jun R. Huh, Christian Mueller, Stuart M. Levitz 2017 University of Massachusetts Medical School

Central Role Of Il-23 And Il-17 Producing Eosinophils As Immunomodulatory Effector Cells In Acute Pulmonary Aspergillosis And Allergic Asthma, Evelyn V. Santos Guerra, Chrono K. Lee, Charles A. Specht, Bhawna Yadav, Haibin Huang, Ali Akalin, Jun R. Huh, Christian Mueller, Stuart M. Levitz

Christian Mueller

Aspergillus fumigatus causes invasive pulmonary disease in immunocompromised hosts and allergic asthma in atopic individuals. We studied the contribution of lung eosinophils to these fungal diseases. By in vivo intracellular cytokine staining and confocal microscopy, we observed that eosinophils act as local sources of IL-23 and IL-17. Remarkably, mice lacking eosinophils had a >95% reduction in the percentage of lung IL-23p19+ cells as well as markedly reduced IL-23 heterodimer in lung lavage fluid. Eosinophils killed A. fumigatus conidia in vivo. Eosinopenic mice had higher mortality rates, decreased recruitment of inflammatory monocytes, and decreased expansion of lung macrophages after challenge with ...


Modeling Hiv Dynamics Following 3bnc117 Antibody Infusion, Samantha Erwin 2017 Virginia Polytechnic Institute and State University

Modeling Hiv Dynamics Following 3bnc117 Antibody Infusion, Samantha Erwin

Biology and Medicine Through Mathematics Conference

No abstract provided.


Characterization Of Severe Malaria In Liberian Children 5 Years Old And Younger, Patricia A. McQuilkin 2017 University of Massachusetts Medical School

Characterization Of Severe Malaria In Liberian Children 5 Years Old And Younger, Patricia A. Mcquilkin

GSBS Dissertations and Theses

Malaria continues to be a challenging problem in the developing world, and the burden of this life threatening disease continues to be borne by young children living in Sub Saharan Africa. One of the biggest challenges to the prevention and control of this problem lies in accurately diagnosing malaria, and distinguishing it from the many other febrile illnesses which present in children in this age group.

Liberia is a West African country with a high burden of malaria. Very little is known about the presentation of severe malaria in children aged 5 years old and younger in Liberia. We undertook ...


Mathematical Modeling For The Transmission Dynamics Of {\It Mycobacterium Marinum} Incorporating Intra-Host Variability, Lihong Zhao 2017 University of Louisiana at Lafayette

Mathematical Modeling For The Transmission Dynamics Of {\It Mycobacterium Marinum} Incorporating Intra-Host Variability, Lihong Zhao

Biology and Medicine Through Mathematics Conference

No abstract provided.


Elucidating The Role Of Interleukin-17a In West Nile Virus Infection, Dhiraj Acharya 2017 University of Southern Mississippi

Elucidating The Role Of Interleukin-17a In West Nile Virus Infection, Dhiraj Acharya

Dissertations

West Nile virus (WNV) is a neurotropic flavivirus of significant public health importance for which no therapeutics and vaccine are currently available. Interleukin-17A (IL-17A) is an inflammatory cytokine that regulates diverse immune functions, while its role is unclear in host’s immune response to WNV. Furthermore, CD8+ T cells are crucial components of immunity and play a vital role in recovery from WNV infection. Here, we report a previously unrecognized function of IL-17A in regulating CD8+ T cell cytotoxicity. We show that WNV induces the expression of IL-17A in both mouse splenocytes and human peripheral blood mononuclear cells cultured in ...


Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte 2017 University of Connecticut - Storrs

Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte

University Scholar Projects

Sickle cell disease (SCD) has been shown to be associated with decreased baseline immunity and thus increased susceptibility to infection. I sought to discern possible causes of this by looking into the correlations between SCD and hematopoiesis, the immune system and the neuroendocrine system, and ultimately by conducting experiments surrounding the impaired immune system of SCD. These experiments focused on the potential causes and effects of the diminution of B-1a cells in the SCD spleen. Adoptive transfers, infections with Streptococcus pneumoniae, and histologic imaging were conducted to establish if the diminution of the B-1a cells in the SCD spleen is ...


A Comparative Analysis Of The West African Hemorrhagic Fevers Caused By The Lassa And Ebola Viruses, Emiene E. Amali-Adekwu 2017 Southeastern University - Lakeland

A Comparative Analysis Of The West African Hemorrhagic Fevers Caused By The Lassa And Ebola Viruses, Emiene E. Amali-Adekwu

Selected Honors Theses

Lassa fever (LF) and Ebola Hemorrhagic Fever (EHF) are viral diseases endemic to West Africa.The etiological agent of Lassa fever is an enveloped virus from the Arenaviridae family and was first discovered in 1969 when two missionary nurses died of a mysterious illness in the town of Lassa in Borno state, Nigeria.1 This virus is animal-borne (zoonotic) and is carried by the animal vector Mastomys natalensis (multimammate rat). The Ebola virus is also zoonotic originating from fruit bats belonging to the Pteropodidae family.2 The first reported case of Ebola Virus Disease (EVD) was a principal who was ...


Creation Of An Immunodeficient Hla-Transgenic Mouse (Humamice) And Functional Validation Of Human Immunity After Transfer Of Hla-Matched Human Cells, Yang Zeng, Bingrun Liu, Marie-Therese Rubio, Xinyue Wang, David M. Ojcius, Ruoping Tang, Antoine Durrbach, Zhitao Ru, Yusen Zhou, Yu-Chun Lone 2017 Beijing Institute of Microbiology and Epidemiology

Creation Of An Immunodeficient Hla-Transgenic Mouse (Humamice) And Functional Validation Of Human Immunity After Transfer Of Hla-Matched Human Cells, Yang Zeng, Bingrun Liu, Marie-Therese Rubio, Xinyue Wang, David M. Ojcius, Ruoping Tang, Antoine Durrbach, Zhitao Ru, Yusen Zhou, Yu-Chun Lone

Dugoni School of Dentistry Faculty Articles

Research on human immunology has been hindered by the lack of optimal small animal models, given that the protective immune responses of human and non-human species show significant differences. However, due to ethical constraints[1] and the high cost of clinical trials, it is urgent to improve the current animal models that can mimic faithfully human physiology, particularly the human immune system (HIS). HIS mice had been generated recently by engrafting human hematopoietic stem cells (hHSCs) or human peripheral mononuclear cells (hPBMCs) into highly immuno-deficient mice such as NSG, NOG or NRG mice. However, a major experimental drawback for studies ...


Validation Of The Pre-B Cell Receptor As A Therapeutic Target In B Cell Precursor Acute Lymphoblastic Leukemia, Michael F. Erasmus 2017 University of New Mexico Medical School

Validation Of The Pre-B Cell Receptor As A Therapeutic Target In B Cell Precursor Acute Lymphoblastic Leukemia, Michael F. Erasmus

Biomedical Sciences ETDs

This dissertation is built upon the fundamental idea that the pre-B cell receptor (pre-BCR) is important to leukemia cell survival and a logical therapeutic target in B cell precursor acute lymphoblastic leukemia (BCP-ALL). The pre-BCR is expressed early at a specific stage during B cell development where it plays a central role in survival of healthy B lymphocytes. This receptor is composed of the membrane heavy chain (mIgμ) associated with surrogate light chain components, 5 and VpreB. Through the use of advanced imaging modalities, in particular two-color single particle tracking (SPT), we showed that pre-BCRs formed transient, homotypic interactions. These ...


Novel Epstein-Barr Virus-Like Particles Incorporating Gh/Gl-Ebna1 Or Gb-Lmp2 Induce High Neutralizing Antibody Titers And Ebv-Specific T-Cell Responses In Immunized Mice, Elizabeth M. Perez, Joslyn Foley, Timelia Tison, Rute Silva, Javier Gordon Ogembo 2017 University of Massachusetts Medical School

Novel Epstein-Barr Virus-Like Particles Incorporating Gh/Gl-Ebna1 Or Gb-Lmp2 Induce High Neutralizing Antibody Titers And Ebv-Specific T-Cell Responses In Immunized Mice, Elizabeth M. Perez, Joslyn Foley, Timelia Tison, Rute Silva, Javier Gordon Ogembo

Open Access Articles

Previous Epstein-Barr virus (EBV) prophylactic vaccines based on the major surface glycoprotein gp350/220 as an immunogen have failed to block viral infection in humans, suggesting a need to target other viral envelope glycoproteins. In this study, we reasoned that incorporating gH/gL or gB, critical glycoproteins for viral fusion and entry, on the surface of a virus-like particle (VLP) would be more immunogenic than gp350/220 for generating effective neutralizing antibodies to prevent viral infection of both epithelial and B cell lines. To boost the humoral response and trigger cell-mediated immunity, EBV nuclear antigen 1 (EBNA1) and latent membrane ...


The Antiviral Rna Interference Response Provides Resistance To Lethal Arbovirus Infection And Vertical Transmission In Caenorhabditis Elegans, Don B. Gammon, Takao Ishidate, Lichao Li, Weifeng Gu, Neal S. Silverman, Craig C. Mello 2017 University of Massachusetts Medical School

The Antiviral Rna Interference Response Provides Resistance To Lethal Arbovirus Infection And Vertical Transmission In Caenorhabditis Elegans, Don B. Gammon, Takao Ishidate, Lichao Li, Weifeng Gu, Neal S. Silverman, Craig C. Mello

University of Massachusetts Medical School Faculty Publications

The recent discovery of the positive-sense single-stranded RNA (ssRNA) Orsay virus (OV) as a natural pathogen of the nematode Caenorhabditis elegans has stimulated interest in exploring virus-nematode interactions. However, OV infection is restricted to a small number of intestinal cells, even in nematodes defective in their antiviral RNA interference (RNAi) response, and is neither lethal nor vertically transmitted. Using a fluorescent reporter strain of the negative-sense ssRNA vesicular stomatitis virus (VSV), we show that microinjection of VSV particles leads to a dose-dependent, muscle tissue-tropic, lethal infection in C. elegans. Furthermore, we find nematodes deficient for components of the antiviral RNAi ...


Delineating Cd4 Dependency Of Hiv-1: Adaptation To Infect Low Level Cd4 Expressing Target Cells Widens Cellular Tropism But Severely Impacts On Envelope Functionality, David Beauparlant, Peter Rusert, Carsten Magnus, Claus Kadelka, Jacqueline Weber, Therese Uhr, Osvaldo Zagordi, Corinna Oberle, Maria J. Duenas-Decamp, Paul R. Clapham, Karin J. Metzner, Huldrych F. Gunthard, Alexandra Trkola 2017 University of Zurich

Delineating Cd4 Dependency Of Hiv-1: Adaptation To Infect Low Level Cd4 Expressing Target Cells Widens Cellular Tropism But Severely Impacts On Envelope Functionality, David Beauparlant, Peter Rusert, Carsten Magnus, Claus Kadelka, Jacqueline Weber, Therese Uhr, Osvaldo Zagordi, Corinna Oberle, Maria J. Duenas-Decamp, Paul R. Clapham, Karin J. Metzner, Huldrych F. Gunthard, Alexandra Trkola

Open Access Articles

A hallmark of HIV-1 infection is the continuously declining number of the virus' predominant target cells, activated CD4+ T cells. With diminishing CD4+ T cell levels, the capacity to utilize alternate cell types and receptors, including cells that express low CD4 receptor levels such as macrophages, thus becomes crucial. To explore evolutionary paths that allow HIV-1 to acquire a wider host cell range by infecting cells with lower CD4 levels, we dissected the evolution of the envelope-CD4 interaction under in vitro culture conditions that mimicked the decline of CD4high target cells, using a prototypic subtype B, R5-tropic strain. Adaptation to ...


Central Role Of Il-23 And Il-17 Producing Eosinophils As Immunomodulatory Effector Cells In Acute Pulmonary Aspergillosis And Allergic Asthma, Evelyn V. Santos Guerra, Chrono K. Lee, Charles A. Specht, Bhawna Yadav, Haibin Huang, Ali Akalin, Jun R. Huh, Christian Mueller, Stuart M. Levitz 2017 University of Massachusetts Medical School

Central Role Of Il-23 And Il-17 Producing Eosinophils As Immunomodulatory Effector Cells In Acute Pulmonary Aspergillosis And Allergic Asthma, Evelyn V. Santos Guerra, Chrono K. Lee, Charles A. Specht, Bhawna Yadav, Haibin Huang, Ali Akalin, Jun R. Huh, Christian Mueller, Stuart M. Levitz

UMass Metabolic Network Publications

Aspergillus fumigatus causes invasive pulmonary disease in immunocompromised hosts and allergic asthma in atopic individuals. We studied the contribution of lung eosinophils to these fungal diseases. By in vivo intracellular cytokine staining and confocal microscopy, we observed that eosinophils act as local sources of IL-23 and IL-17. Remarkably, mice lacking eosinophils had a >95% reduction in the percentage of lung IL-23p19+ cells as well as markedly reduced IL-23 heterodimer in lung lavage fluid. Eosinophils killed A. fumigatus conidia in vivo. Eosinopenic mice had higher mortality rates, decreased recruitment of inflammatory monocytes, and decreased expansion of lung macrophages after challenge with ...


Isolation, Culture And Characterization Of Hirsutella Sinensis Mycelium From Caterpillar Fungus Fruiting Body, Yun-Fei Komi, Jian-Ching Liau, Chien-Sheng Lee, Chen-Yaw Chiu, Jan Martel, Chuan-Sheng Lin, Shan-Fu Tseng, David M. Ojcius, Chia-Chen Lu, Hsin-Chih Lai, John Ding-E. Young 2017 Chang Gung Biotechnology Corporation

Isolation, Culture And Characterization Of Hirsutella Sinensis Mycelium From Caterpillar Fungus Fruiting Body, Yun-Fei Komi, Jian-Ching Liau, Chien-Sheng Lee, Chen-Yaw Chiu, Jan Martel, Chuan-Sheng Lin, Shan-Fu Tseng, David M. Ojcius, Chia-Chen Lu, Hsin-Chih Lai, John Ding-E. Young

Dugoni School of Dentistry Faculty Articles

The caterpillar fungus Ophiocordyceps sinensis (previously called Cordyceps sinensis) has been used for centuries in Asia as a tonic to improve health and longevity. Recent studies show that O. sinensis produces a wide range of biological effects on cells, laboratory animals and humans, including anti-fatigue, anti-infection, anti-inflammatory, antioxidant, and anti-tumor activities. In view of the rarity of O. sinensis fruiting bodies in nature, cultivation of its anamorph mycelium represents a useful alternative for large-scale production. However, O. sinensis fruiting bodies harvested in nature harbor several fungal contaminants, a phenomenon that led to the isolation and characterization of a large number ...


Micrornas Modulate Pathogenesis Resulting From Chlamydial Infection In Mice, Laxmi Yeruva, S. Pouncey, Michael R. Eledge, Sudeepa Bhattacharya, Chunqiao Luo, Erin W. Weatherford, David M. Ojcius, Roger G. Rank 2017 University of Arkansas for Medical Sciences

Micrornas Modulate Pathogenesis Resulting From Chlamydial Infection In Mice, Laxmi Yeruva, S. Pouncey, Michael R. Eledge, Sudeepa Bhattacharya, Chunqiao Luo, Erin W. Weatherford, David M. Ojcius, Roger G. Rank

Dugoni School of Dentistry Faculty Articles

Not all women infected with chlamydiae develop upper genital tract disease, but the reason(s) for this remains undefined. Host genetics and hormonal changes associated with the menstrual cycle are possible explanations for variable infection outcomes. It is also possible that disease severity depends on the virulence of the chlamydial inoculum. It is likely that the inoculum contains multiple genetic variants, differing in virulence. If the virulent variants dominate, then the individual is more likely to develop severe disease. Based on our previous studies, we hypothesized that the relative degree of virulence of a chlamydial population dictates the microRNA (miRNA ...


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