| Interleukin-15 Increases Vaccine Efficacy through a Mechanism Linked to Dendritic Cell Maturation and Enhanced Antibody Titers |
26 NOV 2007 |
8 pages |
| Authors:
Kamal U. Saikh; Teri L. Kissner; Steven Nystrom; Gordon Ruthel; Robert G. Ulrich; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
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 | Interleukin-15 (IL-15) is generally considered to be a growth factor for natural killer cells and for sustaining T-cell memory. Previous data from our laboratory demonstrated that IL-15 is also an important factor for developing human dendritic cells. In this study, we investigated the effect of IL-15 on antibody responses to a recombinant staphylococcal enterotoxin B (SEB) vaccine (STEBVax), in a pre-clinical model of toxic-shock syndrome induced by SEB. We observed ... |
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| Inhibition of Metalloprotease Botulinum Serotype A from a Pseudo-Peptide Binding Mode to a Small Molecule that is Active in Primary Neurons |
16 FEB 2007 |
13 pages |
| Authors:
James C. Burnett; Gordon Ruthel; Christian M. Stegmann; Rekha G. Panchal; Tam L. Nguyen; Ann R. Hermone; Robert G. Stafford; Douglas J. Lane; Tara A. Kenny; Connor F. McGarth; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
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| An efficient research strategy integrating empirically-guided, structure-based modeling and chemoinformatics was used to discover potent small molecule inhibitors of the botulinum neurotoxin serotype A light chain. First, a modeled binding mode for inhibitor 2-mercapto-3-phenylpropionyl-RATKML (K(i) = 330 nM) was generated, and required the use of a molecular dynamic conformer of the enzyme displaying the reorientation of surface loops bordering the substrate binding cleft. These flexible loops are conformationally variable in ... |
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| Anthrax Lethal Toxin Impairs Innate Immune Functions of Alveolar Macrophages and Facilitates Bacillus anthracis Survival |
14 JUN 2006 |
7 pages |
| Authors:
Wilson J. Ribot; Rekha G. Panchal; Katherine C. Brittingham; Gordon Ruthel; Tara A. Kenny; Douglas Lane; Bob Curry; Timothy A. Hoover; Arthur M. Friedlander; Sina Bavari; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
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| Alveolar macrophages (AM) are very important for pulmonary innate immune responses against invading inhaled pathogens because they directly kill the organisms and initiate a cascade of innate and adaptive immune responses. Although several factors contribute to inhalational anthrax, we hypothesized that unimpeded infection of Bacillus anthracis is directly linked to disabling the innate immune functions contributed by AM. Here, we investigated the effects of lethal toxin (LT), one of the ... |
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| Activation of Triggering Receptor Expressed on Myeloid Cells-1 on Human Neutrophils by Marburg and Ebola Viruses |
21 APR 2006 |
11 pages |
| Authors:
Mansour Mohamadzadeh; Sadie S. Coberley; Gene G. Olinger; Warren V. Kalina; Gordon Ruthel; Claudette L. Fullter; Dana L. Swenson; William D. Pratt; Douglas B. Kuhns; Alan L. Schmaljohn; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
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| Marburg virus (MARV) and Ebola virus (EBOV), members of the viral family Filoviridae, cause fatal hemorrhagic fevers in humans and nonhuman primates. High viral burden is coincident with inadequate adaptive immune responses and robust inflammatory responses, and virus-mediated dysregulation of early host defenses has been proposed. Recently, a novel class of innate receptors called the triggering receptors expressed in myeloid cells (TREM) has been discovered and shown to play an ... |
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| Persistence of Zinc-Binding Bacterial Superantigens at the Surface of Antigen-Presenting Cells Contributes to the Extreme Potency of These Superantigens as T-Cell Activators |
SEP 2005 |
10 pages |
| Authors:
Dorothy D. Pless; Gordon Ruthel; Emily K. Reinke; Robert G. Ulrich; Sina Bavari; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
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| Bacterial superantigen intoxication causes massive overactivation of T cells, which can result in potentially lethal toxic shock. Superantigens fall into two groups: superantigens such as staphylococcal enterotoxin B (SEB) that contain a single generic binding site for major histocompatibility complex class II (MHC-II) and more potent superantigens such as SEA with a second, zinc-dependent MHC-II binding site that enables them to cross-link adjacent MHC-II molecules. We found that although all ... |
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| Lactobacilli Activate Human Dendritic Cells that Skew T Cells Toward T Helper 1 Polarization |
06 JAN 2005 |
7 pages |
| Authors:
Mansour Mohamadzadeh; Scott Olson; Warren V. Kalina; Gordon Ruthel; Gretchen L. Demmin; Kelly L. Warfield; Sina Bavari; Todd R. Klaenhammer; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
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| Professional antigen-presenting dendritic cells (DCs) are critical in regulating T cell immune responses at both systemic and mucosal sites. Many Lactobacillus species are normal members of the human gut microflora and most are regarded as safe when administered as probiotics. Because DCs can naturally or therapeutically encounter lactobacilli, we investigated the effects of several well defined strains, representing three species of Lactobacillus on human myeloid DCs (MDCs) and found that ... |
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