Medical Microbiology Commons^™

Apparent Role For Borrelia Burgdorferi Luxs During Mammalian Infection, William K. Arnold, Christina R. Savage, Alyssa D. Antonicello, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The Lyme disease spirochete, Borrelia burgdorferi, controls protein expression patterns during its tick-mammal infection cycle. Earlier studies demonstrated that B. burgdorferi synthesizes 4,5-dihydroxy-2,3-pentanedione (autoinducer-2 [AI-2]) and responds to AI-2 by measurably changing production of several infection-associated proteins. luxS mutants, which are unable to produce AI-2, exhibit altered production of several proteins. B. burgdorferi cannot utilize the other product of LuxS, homocysteine, indicating that phenotypes of luxS mutants are not due to the absence of that molecule. Although a previous study found that a luxS mutant was capable of infecting mice, a critical caveat to those results is that bacterial …

Lipid And Protein Co-Regulation Of Pi3k Effectors Akt And Itk In Lymphocytes, Xinxin Wang, Leonard B. Hills, Yina H. Huang

Dartmouth Scholarship

The phosphoinositide 3-kinase (PI 3-kinase, PI3K) pathway transduces signals critical for lymphocyte function. PI3K generates the phospholipid PIP3 at the plasma membrane to recruit proteins that contain pleckstrin homology (PH) domains - a conserved domain found in hundreds of mammalian proteins. PH domain-PIP3 interactions allow for rapid signal propagation and confer a spatial component to these signals. The kinases Akt and Itk are key PI3K effectors that bind PIP3 via their PH domains and mediate vital processes - such as survival, activation, and differentiation - in lymphocytes. Here, we review the roles and regulation of PI3K signaling in lymphocytes with …

Zhx2 Enhances The Cytotoxicity Of Chemotherapeutic Drugs In Liver Tumor Cells By Repressing Mdr1 Via Interfering With Nf-Ya, Hongxin Ma, Xuetian Yue, Lifen Gao, Xiaohong Liang, Wenjiang Yan, Zhenyu Zhang, Haixia Shan, Hualin Zhang, Brett T. Spear, Chunhong Ma

Microbiology, Immunology, and Molecular Genetics Faculty Publications

We previously reported the tumor suppressor function of Zinc-fingers and homeoboxes 2 (ZHX2) in hepatocellular carcinoma (HCC). Other studies indicate the association of increased ZHX2 expression with improved response to high dose chemotherapy in multiple myeloma. Here, we aim to test whether increased ZHX2 levels in HCC cells repress multidrug resistance 1(MDR1) expression resulting in increased sensitivity to chemotherapeutic drugs. We showed evidence that increased ZHX2 levels correlated with reduced MDR1 expression and enhanced the cytotoxicity of CDDP and ADM in different HCC cell lines. Consistently, elevated ZHX2 significantly reduced ADM efflux in HepG2 cells and greatly increased the CDDP-mediated …

Memory T Cells Specific For Murine Cytomegalovirus Re-Emerge After Multiple Challenges And Recapitulate Immunity In Various Adoptive Transfer Scenarios., Michael Quinn, Holly Turula, Mayank Tandon, Berthony Deslouches, Toktam Moghbeli, Christopher M. Snyder

Department of Microbiology and Immunology Faculty Papers

Reconstitution of CMV-specific immunity after transplant remains a primary clinical objective to prevent CMV disease, and adoptive immunotherapy of CMV-specific T cells can be an effective therapeutic approach. Because of viral persistence, most CMV-specific CD8(+) T cells become terminally differentiated effector phenotype CD8(+) T cells (TEFF). A minor subset retains a memory-like phenotype (memory phenotype CD8(+) T cells [TM]), but it is unknown whether these cells retain memory function or persist over time. Interestingly, recent studies suggest that CMV-specific CD8(+) T cells with different phenotypes have different abilities to reconstitute sustained immunity after transfer. The immunology of human CMV infections …

Two Potential Hookworm Daf-16 Target Genes, Snr-3 And Lpp-1: Gene Structure, Expression Profile, And Implications Of A Cis-Regulatory Element In The Regulation Of Gene Expression, Xin Gao, Kevin Goggin, Camille Dowling, Jason Qian, John Hawdon

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Hookworms infect nearly 700 million people, causing anemia and developmental stunting in heavy infections. Little is known about the genomic structure or gene regulation in hookworms, although recent publication of draft genome assemblies has allowed the first investigations of these topics to be undertaken. The transcription factor DAF-16 mediates multiple developmental pathways in the free living nematode Caenorhabditis elegans, and is involved in the recovery from the developmentally arrested L3 in hookworms. Identification of downstream targets of DAF-16 will provide a better understanding of the molecular mechanism of hookworm infection.

Methods

Genomic Fragment 2.23 containing a DAF-16 binding …

Intake Of Erythrocytes Required For Reproductive Development Of Female Schistosoma Japonicum., Jipeng Wang, Shuqi Wang, Xiufeng Liu, Bin Xu, Riyi Chai, Pan Zhou, Chuan Ju, Jun Sun, Paul J. Brindley, Wei Hu

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The reproductive development and maturation of female schistosomes are crucial since their released eggs are responsible for the host immunopathology and transmission of schistosomiasis. However, little is known about the nutrients required by female Schistosoma japonicum during its sexual maturation. We evaluated the promoting effect of several nutrients (calf serum, red blood cells (RBCs), ATP and hypoxanthine) on the reproductive development of pre-adult females at 18 days post infection (dpi) from mixed infections and at 50 dpi from unisexual infections of laboratory mice in basic medium RPMI-1640. We found RBCs, rather than other nutrients, promoted the female sexual maturation and …

An Improved Method For Generating Axenic Entomopathogenic Nematodes., Shruti Yadav, Upasana Shokal, Steven Forst, Ioannis Eleftherianos

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Steinernema carpocapsae are parasitic nematodes that invade and kill insects. The nematodes are mutualistically associated with the bacteria Xenorhabdus nematophila and together form an excellent model to study pathogen infection processes and host anti-nematode/antibacterial immune responses. To determine the contribution of S. carpocapsae and their associated X. nematophila to the successful infection of insects as well as to investigate the interaction of each mutualistic partner with the insect immune system, it is important to develop and establish robust methods for generating nematodes devoid of their bacteria.

FINDINGS: To produce S. carpocapsae nematodes without their associated X. nematophila bacteria, we …

Of Monkeys And Men: Immunomic Profiling Of Sera From Humans And Non-Human Primates Resistant To Schistosomiasis Reveals Novel Potential Vaccine Candidates., Mark S Pearson, Luke Becker, Patrick Driguez, Neil D Young, Soraya Gaze, Jeffrey M. Bethony, +12 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Schistosoma haematobium affects more than 100 million people throughout Africa and is the causative agent of urogenital schistosomiasis. The parasite is strongly associated with urothelial cancer in infected individuals and as such is designated a group I carcinogen by the International Agency for Research on Cancer. Using a protein microarray containing schistosome proteins, we sought to identify antigens that were the targets of protective IgG1 immune responses in S. haematobium-exposed individuals that acquire drug-induced resistance (DIR) to schistosomiasis after praziquantel treatment. Numerous antigens with known vaccine potential were identified, including calpain (Smp80), tetraspanins, glutathione-S-transferases, and glucose transporters (SGTP1), as well …

The Carcinogenic Liver Fluke Opisthorchis Viverrini Is A Reservoir For Species Of Helicobacter., Raksawan Deenonpoe, Chariya Chomvarin, Chawalit Pairojkul, Yaowalux Chamgramol, Alex Loukas, Paul J. Brindley, Banchob Sripa

Microbiology, Immunology, and Tropical Medicine Faculty Publications

There has been a strong, positive correlation between opisthorchiasis-associated cholangiocarcinoma and infection with Helicobacter. Here a rodent model of human infection with Opisthorchis viverrini was utilized to further investigate relationships of apparent co-infections with O. viverrini and H. pylori. A total of 150 hamsters were assigned to five groups: i) Control hamsters not infected with O. viverrini; ii) O. viverrini-infected hamsters; iii) non-O. viverrini infected hamsters treated with antibiotics (ABx); iv) O. viverrini-infected hamsters treated with ABx; and v) O. viverrini-infected hamsters treated both with ABx and praziquantel (PZQ). Stomach, gallbladder, liver, colonic tissue, colorectal feces and O. viverrini worms …

Comparison Of Findings Using Ultrasonography And Cystoscopy In Urogenital Schistosomiasis In A Public Health Centre In Rural Angola, Julio Santos, Jacinta Chaves, Heriberto Araujo, Nuno Vale, Jose Manuel Costa, Paul J. Brindley, Carlos Lopes, Jean Naples, Clive Shiff, Jorge Dupret, Lucio Lara Santos

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background. Schistosomiasis is a chronic disease caused by infection with parasitic worms of the genus Schistosoma. In sub-Saharan Africa, infections with S. haematobium are most common. Cystoscopic examination (CE) has been accepted as the gold-standard test for detecting the late manifestations of schistosomiasis, including urothelial cancer of the bladder. However, this procedure is invasive and 10 - 40% of tumours may remain undetected. A non-invasive examination and a new generation of biomarkers are needed for better monitoring of the disease.

Objective. To assess the usefulness of ultrasound (US) scans for monitoring of structural urinary tract disease by local public health …

Isolated Candida Infection Of The Lung, Yousef Shweihat Md, James Perry, Darshana T. Shah Phd

Biochemistry and Microbiology

Candida pneumonia is a rare infection of the lungs, with the majority of cases occurring secondary to hematological dissemination of Candida organisms from a distant site, usually the gastrointestinal tract or skin. We report a case of a 77-year-old male who is life-long smoker with a history of rheumatoid arthritis and polymyalgia rheumatica, but did not take immunosuppressants for those conditions. Here, we present an extremely rare case of isolated pulmonary parenchymal Candida infection in the form pulmonary nodules without evidence of systemic disease which has only been described in a few previous reports.

Gene Function In Schistosomes: Recent Advances Toward A Cure, Arnon D. Jurburg, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Anti-Cancer Activity Of Withaferin A In B-Cell Lymphoma., M K Mckenna, B W Gachuki, S S Alhakeem, K N Oben, V M Rangnekar, R C Gupta, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Withaferin A (WA), a withanolide from the plant, Ashwagandha (Withania somnifera) used in Ayurvedic medicine, has been found to be valuable in the treatment of several medical ailments. WA has been found to have anticancer activity against various solid tumors, but its effects on hematological malignancies have not been studied in detail. WA strongly inhibited the survival of several human and murine B cell lymphoma cell lines. Additionally, in vivo studies with syngeneic-graft lymphoma cells suggest that WA inhibits the growth of tumor but does not affect other proliferative tissues. We demonstrate that WA inhibits the efficiency of NF-κB nuclear …

P53 And Cancer-Associated Sialylated Glygans Are Surrogate Markers Of Cancerization Of The Bladder Associated With Schistosoma Haematobium Infection, Julio Santos, Elisabete Fernandes, Jose Alexandre Ferreira, Luis Lima, Ana Tavares, Andreia Peixoto, Beatriz Parreira, Jose Manuel Correia Da Costa, Paul J. Brindley, Carlos Lopes, Lucio L. Santos

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Bladder cancer is a significant health problem in rural areas of Africa and the Middle East where Schistosoma haematobium is prevalent, supporting an association between malignant transformation and infection by this blood fluke. Nevertheless, the molecular mechanisms linking these events are poorly understood. Bladder cancers in infected populations are generally diagnosed at a late stage since there is a lack of non-invasive diagnostic tools, hence enforcing the need for early carcinogenesis markers.

Methodology/Principal Findings

Forty-three formalin-fixed paraffin-embedded bladder biopsies of S. haematobium-infected patients, consisting of bladder tumours, tumour adjacent mucosa and pre-malignant/malignant urothelial lesions, were screened for bladder …

The Mirnaome Of Opisthorchis Viverrini Induced Intrahepatic Cholangiocarcinoma, Jin Peng, Yanjun Feng, Gabriel Rinaldi, Ponlapat Yonglitthipagon, Samantha Easley, Therawach Laha, Chawalit Pairojkul, Vajarabhongsa Bhudhisawasdi, Banchob Sripa, Paul J. Brindley, Jason P. Mulvenna, Jeffrey M. Bethony, Jordan L. Plieskatt

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer, arising in the biliary ducts that extend into the liver. The highest incidence of ICC occurs in Southeast Asia, particularly in the Mekong River Basin countries of Thailand, Laos, Cambodia, and Vietnam, where it is strongly associated with chronic infection by the food-borne liver fluke Opisthorchis viverrini (OV), one of only three eukaryote pathogens considered Group one carcinogens. Intrahepatic cholangiocarcinoma is usually diagnosed at an advanced stage, with a poor prognosis and survival often less than 24 months. Hence, biomarkers that enable the early detection of ICC would be desirable and have a …

Profiling Mirnas In Nasopharyngeal Carcinoma Ffpe Tissue By Microarray And Next Generation Sequencing, Jin Peng, Yanjun Feng, Gabriel Rinaldi, Paul H. Levine, Samantha Easley, Elizabeth Martinez, Salman Hashmi, Nader Sadeghi, Paul J. Brindley, Jason P. Mulvenna, Jeffrey M. Bethony, Jordan L. Plieskatt

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Nasopharyngeal carcinoma (NPC) is a non-lymphomatous, squamous-cell carcinoma that occurs in the epithelial lining of the nasopharynx. Nasopharyngeal carcinoma has a geographically well-defined distribution worldwide, with the highest prevalence in China, Southeast Asia, and Northern Africa. Symptoms of nascent NPC may be unapparent or trivial, with diagnosis based on the histopathology of biopsied tissue following endoscopy of the nasopharynx. The tumor node metastasis (TNM) staging system is the benchmark for the prognosis of NPC and guides treatment strategy. However, there is a consensus that the TNM system is not sufficiently specific for the prognosis of NPC, as it does not …

Impact Of Gender On The Decision To Participate In A Clinical Trial: A Cross-Sectional Study, Lucas Lobato, Jeffrey M. Bethony, Fernanda Bicalho Pereira, Shannon Lee Grahek, David J. Diemert, Maria Flavia Gazzinelli

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

In order for Informed Consent to be ethical and valid each clinical trial participant must be able to make a voluntary decision to participate, free from pressure or coercion. Nonetheless, many factors may influence the decision reached, and such influences may be different for male and female volunteers. Being aware of these differences may help researches develop better processes for obtaining consent that safeguard the right of autonomy for all participants. The goal of this study was to evaluate potential gender-based differences in the factors influencing clinical trial participation.

Methods

This cross-sectional study was conducted in the Northeast region …

Chip-Seq And In Vivo Transcriptome Analyses Of The Aspergillus Fumigatus Srebp Srba Reveals A New Regulator Of The Fungal Hypoxia Response And Virulence, Dawoon Chung, Bridget M. Barker, Charles C. Carey, Brittney Merriman

Dartmouth Scholarship

The Aspergillus fumigatus sterol regulatory element binding protein (SREBP) SrbA belongs to the basic Helix-Loop-Helix (bHLH) family of transcription factors and is crucial for antifungal drug resistance and virulence. The latter phenotype is especially striking, as loss of SrbA results in complete loss of virulence in murine models of invasive pulmonary aspergillosis (IPA). How fungal SREBPs mediate fungal virulence is unknown, though it has been suggested that lack of growth in hypoxic conditions accounts for the attenuated virulence. To further understand the role of SrbA in fungal infection site pathobiology, chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) was …

Caspase-3 Mediates The Pathogenic Effect Of Yersinia Pestis Yopm In Liver Of C57bl/6 Mice And Contributes To Yopm's Function In Spleen, Zhan Ye, Amanda A. Gorman, Annette M. Uittenbogaard, Tanya Myers-Morales, Alan M. Kaplan, Donald A. Cohen, Susan C. Straley

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The virulence protein YopM of the plague bacterium Yersinia pestis has different dominant effects in liver and spleen. Previous studies focused on spleen, where YopM inhibits accumulation of inflammatory dendritic cells. In the present study we focused on liver, where PMN function may be directly undermined by YopM without changes in inflammatory cell numbers in the initial days of infection, and foci of inflammation are easily identified. Mice were infected with parent and ΔyopM-1 Y. pestis KIM5, and effects of YopM were assessed by immunohistochemistry and determinations of bacterial viable numbers in organs. The bacteria were found …

Strengthening Neglected Tropical Disease Research Through Enhancing Research-Site Capacity: An Evaluation Of A Novel Web Application To Facilitate Research Collections, Tanzin Furtado, Samuel Franzen, Francois Van Loggerenberg, Gwenaelle Carn, Shannon Grahek, Megan Mcbride, Maureen Power, Barbara Savarese, Margaret Ann Snowden, Gwynn Stevens, Almarie Uys, Trudie Lang

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Assessment Of Anthelmintic Efficacy Of Mebendazole In School Children In Six Countries Where Soil-Transmitted Helminths Are Endemic, Bruno Levecke, Antonio Montresor, Marco Albonico, Shaali M. Ame, Jerzy M. Behnke, Jeffrey M. Bethony, +15 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND:

Robust reference values for fecal egg count reduction (FECR) rates of the most widely used anthelmintic drugs in preventive chemotherapy (PC) programs for controlling soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura, and hookworm) are still lacking. However, they are urgently needed to ensure detection of reduced efficacies that are predicted to occur due to growing drug pressure. Here, using a standardized methodology, we assessed the FECR rate of a single oral dose of mebendazole (MEB; 500 mg) against STHs in six trials in school children in different locations around the world. Our results are compared with those previously obtained …

Hiv-1 Infection Of Macrophages Induces Retention Of Cholesterol Transporter Abca1 In The Endoplasmic Reticulum, Beda Brichacek, Christina Darwish, Anastas Popratiloff, Larisa Dubrovsky, Michael I. Bukrinsky

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Differential Spatial Repositioning Of Activated Genes In Biomphalaria Glabrata Snails Infected With Schistosoma Mansoni, Halime D. Arican-Goktas, Wannaporn Ittiprasert, Joanna M. Bridger, Matty Knight

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Schistosomiasis is an infectious disease infecting mammals as the definitive host and fresh water snails as the intermediate host. Understanding the molecular and biochemical relationship between the causative schistosome parasite and its hosts will be key to understanding and ultimately treating and/or eradicating the disease. There is increasing evidence that pathogens that have co-evolved with their hosts can manipulate their hosts' behaviour at various levels to augment an infection. Bacteria, for example, can induce beneficial chromatin remodelling of the host genome. We have previously shown in vitro thatBiomphalaria glabrata embryonic cells co-cultured with schistosome miracidia display genes changing their …

Diminished Humoral Responses Against And Reduced Gene Expression Levels Of Human Endogenous Retrovirus-K (Herv-K) In Psoriasis, Rashmi Gupta, Henri-Alexandre Michaud, Xue Zeng, Maya Debbaneh, Sarah T. Arron, R. Brad Jones, Christopher E. Ormsby, Douglas F. Nixon, Wilson Liao

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Vaccination With A Genetically Modified Brugia Malayi Cysteine Protease Inhibitor-2 Reduces Adult Parasite Numbers And Affects The Fertility Of Female Worms Following A Subcutaneous Challenge Of Mongolian Gerbils (Meriones Unguiculatus) With B. Malayi Infective Larvae., Sridhar Arumugam, Junfei Wei, Danielle Ward, David Abraham, Sara Lustigman, Bin Zhan, Thomas R. Klei

Department of Microbiology and Immunology Faculty Papers

Vaccination of Mongolian gerbils with Brugia malayi cysteine protease inhibitor-2 in which the amino acid Asn66 was mutated to Lys66 (Bm-CPI-2M) resulted in reduced parasite numbers of 48.6% and 48.0% at 42 and 90 days p.i. with B. malayi L3s. Fertility of female worms was also affected at 90 days p.i. In vitro killing of L3s observed in the presence of gerbil peritoneal exudate cells and anti-Bm-CPI-2M sera suggests antibody-dependent cell-mediated cytotoxicity as a putative protective mechanism. These observations suggest that Bm-CPI-2M is a promising prophylactic and anti-fecundity vaccine candidate.

Cyclic Di-Gmp-Dependent Signaling Pathways In The Pathogenic Firmicute Listeria Monocytogenes, Li-Hong Chen, Volkan K. Köseoğlu, Zehra T. Güvener, Tanya Myers-Morales, Joseph M. Reed, Sarah E. F. D'Orazio, Kurt W. Miller, Mark Gomelsky

Microbiology, Immunology, and Molecular Genetics Faculty Publications

We characterized key components and major targets of the c-di-GMP signaling pathways in the foodborne pathogen Listeria monocytogenes, identified a new c-di-GMP-inducible exopolysaccharide responsible for motility inhibition, cell aggregation, and enhanced tolerance to disinfectants and desiccation, and provided first insights into the role of c-di-GMP signaling in listerial virulence. Genome-wide genetic and biochemical analyses of c-di-GMP signaling pathways revealed that L. monocytogenes has three GGDEF domain proteins, DgcA (Lmo1911), DgcB (Lmo1912) and DgcC (Lmo2174), that possess diguanylate cyclase activity, and three EAL domain proteins, PdeB (Lmo0131), PdeC (Lmo1914) and PdeD (Lmo0111), that possess c-di-GMP phosphodiesterase activity. Deletion of all phosphodiesterase …

Cyclic Di-Gmp-Dependent Signaling Pathways In The Pathogenic Firmicute Listeria Monocytogenes, Li-Hong Chen, Volkan K. Köseoğlu, Zehra T. Güvener, Tanya Myers-Morales, Joseph M. Reed, Sarah E. F. D'Orazio, Kurt W. Miller, Mark Gomelsky

Microbiology, Immunology, and Molecular Genetics Faculty Publications

We characterized key components and major targets of the c-di-GMP signaling pathways in the foodborne pathogen Listeria monocytogenes, identified a new c-di-GMP-inducible exopolysaccharide responsible for motility inhibition, cell aggregation, and enhanced tolerance to disinfectants and desiccation, and provided first insights into the role of c-di-GMP signaling in listerial virulence. Genome-wide genetic and biochemical analyses of c-di-GMP signaling pathways revealed that L. monocytogenes has three GGDEF domain proteins, DgcA (Lmo1911), DgcB (Lmo1912) and DgcC (Lmo2174), that possess diguanylate cyclase activity, and three EAL domain proteins, PdeB (Lmo0131), PdeC (Lmo1914) and PdeD (Lmo0111), that possess c-di-GMP phosphodiesterase activity. Deletion of all …

Vaccines To Combat River Blindness: Expression, Selection And Formulation Of Vaccines Against Infection With Onchocerca Volvulus In A Mouse Model., Jessica A. Hess, Bin Zhan, Sandra Bonne-Annee, Jessica M. Deckman, Maria Elena Bottazzi, Peter J. Hotez, Thomas R R. Klei, Sara Lustigman, David Abraham

Department of Microbiology and Immunology Faculty Papers

Human onchocerciasis is a neglected tropical disease caused by Onchocerca volvulus and an important cause of blindness and chronic disability in the developing world. Although mass drug administration of ivermectin has had a profound effect on control of the disease, additional tools are critically needed including the need for a vaccine against onchocerciasis. The objectives of the present study were to: (i) select antigens with known vaccine pedigrees as components of a vaccine; (ii) produce the selected vaccine antigens under controlled conditions, using two expression systems and in one laboratory and (iii) evaluate their vaccine efficacy using a single immunisation …

Vcam-1/Α4Β1 Integrin Interaction Is Crucial For Prompt Recruitment Of Immune T Cells Into The Brain During The Early Stage Of Reactivation Of Chronic Infection With Toxoplasma Gondii To Prevent Toxoplasmic Encephalitis, Qila Sa, Eri Ochiai, Tomoko Sengoku, Melinda E. Wilson, Morgan Brogli, Stephen Crutcher, Sara A. Michie, Baohui Xu, Laura Payne, Xisheng Wang, Yasuhiro Suzuki

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Reactivation of chronic infection with Toxoplasma gondii can cause life-threatening toxoplasmic encephalitis in immunocompromised individuals. We examined the role of VCAM-1/α4β1 integrin interaction in T cell recruitment to prevent reactivation of the infection in the brain. SCID mice were infected and treated with sulfadiazine to establish a chronic infection. VCAM-1 and ICAM-1 were the endothelial adhesion molecules detected on cerebral vessels of the infected SCID and wild-type animals. Immune T cells from infected wild-type mice were treated with anti-α4 integrin or control antibodies and transferred into infected SCID or nude mice, and the animals received the same antibody every other …

Systemic Hematogenous Maintenance Of Memory Inflation By Mcmv Infection., Corinne J Smith, Holly Turula, Christopher M. Snyder

Department of Microbiology and Immunology Faculty Papers

Several low-grade persistent viral infections induce and sustain very large numbers of virus-specific effector T cells. This was first described as a response to cytomegalovirus (CMV), a herpesvirus that establishes a life-long persistent/latent infection, and sustains the largest known effector T cell populations in healthy people. These T cells remain functional and traffic systemically, which has led to the recent exploration of CMV as a persistent vaccine vector. However, the maintenance of this remarkable response is not understood. Current models propose that reservoirs of viral antigen and/or latently infected cells in lymph nodes stimulate T cell proliferation and effector differentiation, …