A5079337385- Viral Infections and Vectors
- Mosquito-borne diseases and control
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- SARS-CoV-2 and COVID-19 Research
- Viral Infections and Outbreaks Research
- COVID-19 Clinical Research Studies
- Bacillus and Francisella bacterial research
- Immunotherapy and Immune Responses
- Reproductive tract infections research
- Immune responses and vaccinations
- Vector-Borne Animal Diseases
- Virus-based gene therapy research
- Virology and Viral Diseases
- Phagocytosis and Immune Regulation
- Vector-borne infectious diseases
- Parasitic Diseases Research and Treatment
- Urinary Tract Infections Management
- Yersinia bacterium, plague, ectoparasites research
- HIV Research and Treatment
- Long-Term Effects of COVID-19
- Immune Response and Inflammation
- Vibrio bacteria research studies
- Reproductive System and Pregnancy
- Antimicrobial Resistance in Staphylococcus
National Institute of Allergy and Infectious Diseases
2016-2025
National Institutes of Health
2016-2025
Rocky Mountain Research (United States)
2010-2022
Genomics (United Kingdom)
2010
Heska (United States)
1999-2000
University of Colorado Health
2000
GTx (United States)
2000
Abstract Acute inflammatory lung injury is often a delayed complication of critical illness and associated with increased mortality. High mobility group-1 (HMG-1) protein, in addition to its role as transcriptional regulatory factor, has recently been identified late mediator endotoxin lethality. In the present studies, HMG-1 given intratracheally produced acute lungs, neutrophil accumulation, development edema, pulmonary production IL-1β, TNF-α, macrophage-inflammatory protein-2....
Acute lung injury is characterized by accumulation of neutrophils in the lungs, accompanied development interstitial edema and an intense inflammatory response. To assess role as early immune effectors hemorrhage- or endotoxemia-induced injury, mice were made neutropenic with cyclophosphamide anti-neutrophil antibodies. Endotoxemia- hemorrhage-induced was significantly reduced animals. Activation transcriptional regulatory factor nuclear factor-κB after hemorrhage endotoxemia diminished...
ChAdOx1 nCoV-19/AZD1222 is an approved adenovirus-based vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) currently being deployed globally. Previous studies in rhesus macaques revealed that intramuscular vaccination with provided protection against pneumonia but did not reduce shedding of SARS-CoV-2 from the upper tract. Here, we investigated whether intranasally administered nCoV-19 reduces detection virus nasal swabs after challenging vaccinated and hamsters...
Flaviviruses transmitted by arthropods represent a tremendous disease burden for humans, causing millions of infections annually. All vector-borne flaviviruses studied to date suppress host innate responses infection inhibiting alpha/beta interferon (IFN-alpha/beta)-mediated JAK-STAT signal transduction. The viral nonstructural protein NS5 some functions as the major IFN antagonist, associated with inhibition IFN-dependent STAT1 phosphorylation (pY-STAT1) or STAT2 degradation. West Nile...
Infections with the leading nosocomial pathogen Staphylococcus epidermidis are characterized by biofilm development on indwelling medical devices. We demonstrate that quorum-sensing regulator agr affects of S. in an unexpected fashion and is likely involved promoting detachment. An isogenic mutant showed increased colonization a rabbit model. In addition, nonfunctional occurred more frequently among strains isolated from infections joint prostheses. Lack functionality was based mutations,...
Salmonella invade non-phagocytic cells by inducing massive actin rearrangements, resulting in membrane ruffle formation and phagocytosis of the bacteria. This process is mediated a cohort effector proteins translocated into host cell type III secretion system 1, which encoded genes pathogenicity island (SPI) 1 regulon. network precisely regulated must be induced outside cells. In vitro invasive are prepared growth synthetic media although details vary. Here, we show that culture conditions...
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) likely originated in bats and passed to humans through dromedary camels; however, the genetic mechanisms underlying cross-species adaptation remain poorly understood. Variation host receptor, dipeptidyl peptidase 4 (DPP4), can block interaction with MERS-CoV spike protein form a species barrier infection. To better understand adaptability of MERS-CoV, we identified suboptimal species-derived variant DPP4 study viral adaption. Passaging...
Abstract The recent association between Zika virus (ZIKV) and neurologic complications, including Guillain-Barré syndrome in adults CNS abnormalities fetuses, highlights the importance understanding immunological mechanisms controlling this emerging infection. Studies have indicated that ZIKV evades human type I IFN response, suggesting a role for adaptive immune response resolving However, inability of to antagonize mouse renders highly susceptible circulating murine models. Thus, as we...
Chlamydia trachomatis is a human pathogen associated with significant morbidity worldwide. As obligate intracellular parasites, chlamydiae must survive within eukaryotic cells for sufficient time to complete their developmental cycle. To promote host cell survival, express poorly understood anti-apoptotic factors. Using recently developed genetic tools, we show that three inclusion membrane proteins (Incs) out of eleven examined are required stability and avoidance death pathways. In the...
Phenol-soluble modulin (PSM) is a peptide complex produced by the nosocomial pathogen Staphylococcus epidermidis that has strong capacity to activate human innate immune response. We developed novel method based on liquid chromatography-mass spectrometry (LC-MS) quantify production of individual PSM components. Each was abundant in most 76 S strains tested. Importantly, none components were secreted an agr mutant strain, indicating synthesis regulated strictly quorum-sensing system....
Abstract Intramuscular vaccination with ChAdOx1 nCoV-19/AZD1222 protected rhesus macaques against pneumonia but did not reduce shedding of SARS-CoV-2. Here we investigate whether intranasally administered nCoV-19 reduces shedding, using a SARS-CoV-2 virus the D614G mutation in spike protein. Viral load swabs obtained from vaccinated hamsters was significantly decreased compared to controls and no viral RNA or infectious found lung tissue, both direct challenge transmission model. Intranasal...
Friend virus (FV) and lactate dehydrogenase-elevating (LDV) are endemic mouse viruses that can cause long-term chronic infections in mice. We found numerous mouse-passaged FV isolates also contained LDV coinfection with delayed FV-specific CD8(+) T-cell responses during acute infection. While did not alter the type of pathology induced by FV, which was severe splenomegaly caused erythroproliferation, immunosuppression mediated increased both severity duration Compared to mice infected alone,...
ABSTRACT The majority of human Yersinia pestis infections result from introduction bacteria into the skin by bite an infected flea. Once in dermis, Y. can evade host’s innate immune response and subsequently disseminate to draining lymph node (dLN). There, pathogen replicates large numbers, causing pathognomonic bubo bubonic plague. In this study, several cytometric microscopic techniques were used characterize early host intradermal (i.d.) infection. Mice i.d. with fully virulent or...
Salmonella enterica serovar Typhimurium is a common cause of food-borne gastrointestinal illness, but additionally it causes potentially fatal bacteremia in some immunocompromised patients. In mice, systemic spread and replication the bacteria depend upon infection within macrophages, human macrophages not widely reported or well studied. order to assess ability replicate we infected primary monocyte-derived (MDM) that had been differentiated under conditions known generate different...
Tick-borne encephalitis virus (TBEV), a member of the Flaviviridae family, is leading cause viral in Europe and Asia. Dendritic cells (DCs), as early cellular targets infection, provide an opportunity for flaviviruses to inhibit innate adaptive immune responses. Flaviviruses modulate DC function, but mechanisms underpinning this are not defined. We examined maturation phenotype function murine bone marrow-derived DCs infected with Langat (LGTV), naturally attenuated TBEV serogroup. LGTV...
Abstract Prolonged exposure of CD8 + T cells to antigenic stimulation, as in chronic viral infections, leads a state diminished function termed exhaustion. We now demonstrate that even during exhaustion there is subset functional defined by surface expression SIRPα, protein not previously reported on lymphocytes. On SIRPα cells, co-inhibitory receptors counterbalanced co-stimulatory and it only actively proliferate, transcribe IFNγ show cytolytic activity. Furthermore, target express the...
Severe coronavirus disease 2019 (COVID-19) has been associated with T cell lymphopenia, but no causal effect of deficiency on severity established. To investigate the specific role cells in recovery from severe acute respiratory syndrome 2 (SARS-CoV-2) infections, we studied rhesus macaques that were depleted either CD4+, CD8+, or both subsets prior to infection. Peak virus loads similar all groups, resolution cell-depleted animals was slightly delayed compared controls. The groups developed...
Advanced age is a key predictor of severe COVID-19. To gain insight into this relationship, we used the rhesus macaque model SARS-CoV-2 infection. Eight older and eight younger macaques were inoculated with SARS-CoV-2. Animals evaluated using viral RNA quantification, clinical observations, thoracic radiographs, single-cell transcriptomics, multiparameter flow cytometry, multiplex immunohistochemistry, cytokine detection, lipidomics analysis at predefined time points in various tissues....
Abstract Borrelia burgdorferi , the causative agent of Lyme disease, is well known for its unique morphology, physiology, and enzootic lifecycle. Building on previous work that showed peptide transport essential viability, we endeavored to more clearly define impact starvation spirochete directly compare targeted free amino acid starvation. Herein, confirm ability a putative GltP, BB0401, facilitate glutamate aspartate as demonstrate requirement cell growth motility. Using conditional...
Abstract Ebola virus (EBOV) and Marburg (MARV) are zoonotic filoviruses that cause hemorrhagic fever in humans. Correlative data implicate bats as natural EBOV hosts, but neither a full-length genome nor an isolate has been found any sampled. Here, we model filovirus infection the Jamaican fruit bat (JFB), Artibeus jamaicensis, by inoculation with either or MARV through combination of oral, intranasal, subcutaneous routes. Infection results systemic replication oral shedding infectious...
Abstract Regulatory T cell (Treg)-mediated suppression of CD8+ cells has been implicated in the establishment and maintenance chronic viral infections, but little is known about mechanism suppression. In this study an vitro assay was developed to investigate by Friend retrovirus (FV)-induced Tregs. CD4+CD25+ isolated from mice chronically infected with FV suppressed development effector function naive without affecting their ability proliferate or up-regulate activation markers....
ABSTRACT A delayed inflammatory response is a prominent feature of infection with Yersinia pestis , the agent bubonic and pneumonic plague. Using rat model plague, we examined lymph node histopathology, transcriptome, extracellular cytokine levels to broadly characterize kinetics extent host Y. how it influenced by virulence plasmid (pYV). Remarkably, dissemination multiplication wild-type during stage disease did not induce any detectable gene expression or cells in developing bubo. Only...
It is well understood that the adaptive immune response to infectious agents includes a modulating suppressive component as an activating component. We now show very early innate also has immunosuppressive Infected cells upregulate CD47 "don't eat me" signal, which slows phagocytic uptake of dying and viable downstream antigen-presenting cell (APC) functions. A mimic acts essential virulence factor encoded by all poxviruses, but expression on infected was found be upregulated even pathogens,...
La Crosse virus (LACV) is the leading cause of pediatric arboviral encephalitis in USA. LACV can result learning and memory deficits, which may be due to infection apoptosis neurons brain. Despite being primary cell infected brain by LACV, little known about neuronal responses infection.Human cerebral organoids (COs), contain a spectrum developing neurons, were used examine LACV. Plaque assay quantitative reverse transcription (qRT) PCR determine susceptibility COs infection....