Medicine and Health Sciences Commons^™

Development Of Onchocerca Volvulus In Humanized Nsg Mice And Detection Of Parasite Biomarkers In Urine And Serum., John B. Patton, Sasisekhar Bennuru, Mark L. Eberhard, Jessica A. Hess Ligas, April R. Torigian, Sara Lustigman, Thomas B. Nutman, David Abraham

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: The study of Onchocerca volvulus has been limited by its host range, with only humans and non-human primates shown to be susceptible to the full life cycle infection. Small animal models that support the development of adult parasites have not been identified.

METHODOLOGY/PRINCIPAL FINDINGS: We hypothesized that highly immunodeficient NSG mice would support the survival and maturation of O. volvulus and alteration of the host microenvironment through the addition of various human cells and tissues would further enhance the level of parasite maturation. NSG mice were humanized with: (1) umbilical cord derived CD34+ stem cells, (2) fetal derived liver, …

A Virus-Encoded Type I Interferon Decoy Receptor Enables Evasion Of Host Immunity Through Cell-Surface Binding., Bruno Hernáez, Juan Manuel Alonso-Lobo, Imma Montanuy, Cornelius Fischer, Sascha Sauer, Luis J. Sigal, Noemí Sevilla, Antonio Alcamí

Department of Microbiology and Immunology Faculty Papers

Soluble cytokine decoy receptors are potent immune modulatory reagents with therapeutic applications. Some virus-encoded secreted cytokine receptors interact with glycosaminoglycans expressed at the cell surface, but the biological significance of this activity in vivo is poorly understood. Here, we show the type I interferon binding protein (IFNα/βBP) encoded by vaccinia and ectromelia viruses requires of this cell binding activity to confer full virulence to these viruses and to retain immunomodulatory activity. Expression of a variant form of the IFNα/βBP that inhibits IFN activity, but does not interact with cell surface glycosaminoglycans, results in highly attenuated viruses with a virulence similar …

Role Of The Fractalkine Receptor In Cns Autoimmune Inflammation: New Approach Utilizing A Mouse Model Expressing The Human Cx3cr1, Sandra M. Cardona, Sangwon V. Kim, Kaira A. Church, Vanessa O. Torres, Ian A. Cleary, Andrew S. Mendiola, Stephen P. Saville, Stephanie S. Watowich, Jan Parker-Thornburg, Alejandro Soto-Ospina, Pedronel Araque, Richard M. Ransohoff, Astrid E. Cardona

Department of Microbiology and Immunology Faculty Papers

Multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS) is the leading cause of non-traumatic neurological disability in young adults. Immune mediated destruction of myelin and oligodendrocytes is considered the primary pathology of MS, but progressive axonal loss is the major cause of neurological disability. In an effort to understand microglia function during CNS inflammation, our laboratory focuses on the fractalkine/CX3CR1 signaling as a regulator of microglia neurotoxicity in various models of neurodegeneration. Fractalkine (FKN) is a transmembrane chemokine expressed in the CNS by neurons and signals through its unique receptor CX3CR1 present in microglia. During …

Polymicrobial Sepsis Influences Nk-Cell-Mediated Immunity By Diminishing Nk-Cell-Intrinsic Receptor-Mediated Effector Responses To Viral Ligands Or Infections., Isaac J. Jensen, Christina S. Winborn, Micaela G. Fosdick, Peng Shao, Mikaela M. Tremblay, Qiang Shan, Sandeep Kumar Tripathy, Christopher M. Snyder, Hai-Hui Xue, Thomas S. Griffith, Jon C. Houtman, Vladimir P. Badovinac

Department of Microbiology and Immunology Faculty Papers

The sepsis-induced cytokine storm leads to severe lymphopenia and reduced effector capacity of remaining/surviving cells. This results in a prolonged state of immunoparalysis, that contributes to enhanced morbidity/mortality of sepsis survivors upon secondary infection. The impact of sepsis on several lymphoid subsets has been characterized, yet its impact on NK-cells remains underappreciated-despite their critical role in controlling infection(s). Here, we observed numerical loss of NK-cells in multiple tissues after cecal-ligation-and-puncture (CLP)-induced sepsis. To elucidate the sepsis-induced lesions in surviving NK-cells, transcriptional profiles were evaluated and indicated changes consistent with impaired effector functionality. A corresponding deficit in NK-cell capacity to produce …

With Some Risk-Taking And Luck: A Veterinarian's Adventures In Viral Immunology., Luis J. Sigal

Department of Microbiology and Immunology Faculty Papers

No abstract provided.

Cd8+ T-Cell Responses In Vaccination: Reconsidering Targets And Function In The Context Of Chronic Antigen Stimulation, Gabriela L. Cosma, Laurence Eisenlohr

Department of Microbiology and Immunology Faculty Papers

Cytotoxic CD8 T cells play important roles in eliminating infected and transformed cells. Owing to their potential for therapeutic applications, significant efforts are dedicated toward developing CD8 T cell-based vaccines. Thus far, CD8 T-cell vaccination strategies have had limited success therapeutically in contrast to those targeting antibody-based immunity. However, if the current challenges and gaps in the understanding of T-cell biology are overcome, the full potential of rational CD8 T-cell vaccine design might be realized. Here, we review recent progress in this direction, focusing on target selection and maintenance of function in the settings of chronic infections and cancers.

Onchocerca Volvulus: The Road From Basic Biology To A Vaccine., Sara Lustigman, Benjamin L. Makepeace, Thomas R. Klei, Simon A. Babayan, Peter Hotez, David Abraham, Maria Elena Bottazzi

Department of Microbiology and Immunology Faculty Papers

Human onchocerciasis - commonly known as river blindness - is one of the most devastating yet neglected tropical diseases, leaving many millions in sub-Saharan Africa blind and/or with chronic disabilities. Attempts to eliminate onchocerciasis, primarily through the mass drug administration of ivermectin, remains challenging and has been heightened by the recent news that drug-resistant parasites are developing in some populations after years of drug treatment. Needed, and needed now, in the fight to eliminate onchocerciasis are new tools, such as preventive and therapeutic vaccines. This review summarizes the progress made to advance the onchocerciasis vaccine from the research laboratory into …