A5011849894- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Tuberculosis Research and Epidemiology
- Long-Term Effects of COVID-19
- Respiratory viral infections research
- Mycobacterium research and diagnosis
- Diabetes and associated disorders
- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Asthma and respiratory diseases
- Cell Adhesion Molecules Research
- Nanoplatforms for cancer theranostics
- Parasitic infections in humans and animals
- interferon and immune responses
- Neonatal and Maternal Infections
- Virus-based gene therapy research
- Bacterial Infections and Vaccines
- Celiac Disease Research and Management
- Ocular Disorders and Treatments
- Blood disorders and treatments
National Institute of Allergy and Infectious Diseases
2020-2024
National Institutes of Health
2020-2024
University of Minnesota
1973-2024
La Jolla Institute for Immunology
2024
Fundação Oswaldo Cruz
2024
University of California, San Diego
2024
University of Cape Town
2024
Children's Medical Research Institute
2023
University of Minnesota Medical Center
2011-2016
Ministry of Forests
2015
Abstract The immunosuppressive tumor microenvironment limits the success of current immunotherapies. host retains memory T cells specific for previous infections throughout entire body that are capable executing potent and immediate immunostimulatory functions. Here we show virus-specific extend their surveillance to mouse human tumors. Reactivating these antiviral can arrest growth checkpoint blockade-resistant poorly immunogenic tumors in mice after injecting adjuvant-free non-replicating...
Blockade of the PD-1 coinhibitory pathway compromises immune control Mycobacterium tuberculosis infection in rhesus macaques.
Adoptive transfer of thymus-derived natural regulatory T cells (nTregs) effectively suppresses disease in murine models autoimmunity and graft-versus-host (GVHD). TGFß induces Foxp3 expression suppressive function stimulated CD4+25- cells, these induced Treg (iTregs), like nTreg, suppress auto- allo-reactivity vivo. However, while human the expanded lack suppressor cell function. Here we show that Rapamycin (Rapa) enhances TGFß-dependent a potent naive (CD4+ 25-45RA+) cells. Rapa/TGFß iTregs...
Mucosal-associated invariant T (MAIT) cells are potential targets of vaccination and host-directed therapeutics for tuberculosis, but the role MAIT during Mycobacterium tuberculosis (Mtb) infection in vivo is not well understood. Here we find that following Mtb mount minimal responses, cell-deficient MR1−/− mice display normal survival. Preinfection expansion through 5-OP-RU fails to protect against subsequent challenge. In fact, delays Mtb-specific CD4 cell priming lung-draining lymph...
Host resistance to Mycobacterium tuberculosis (Mtb) infection requires the activities of multiple leukocyte subsets, yet roles different innate effector cells during are incompletely understood. Here we uncover an unexpected association between eosinophils and Mtb infection. In humans, decreased in blood but enriched resected human lung lesions autopsy granulomas. An influx is also evident infected zebrafish, mice, nonhuman primate granulomas, where they functionally activated degranulate....
Abstract Mucosal tissues are subject to frequent pathogen exposure and major sites for transmission of infectious disease. CD8 T cells play a critical role in controlling mucosa-acquired infections even though their migration into mucosal is tightly regulated. The mechanisms signals that control the formation tissue-resident memory poorly understood; however, one key regulator cell differentiation, mammalian target rapamycin kinase, can be inhibited by rapamycin. We report that, despite...
SARS-CoV-2 primarily replicates in mucosal sites, and more information is needed about immune responses infected tissues. Here, we used rhesus macaques to model protective primary tissues during mild COVID-19. Viral RNA levels were highest on days 1-2 post-infection fell precipitously thereafter.
The regulation of inflammatory responses and pulmonary disease during SARS-CoV-2 infection is incompletely understood. Here we examine the roles prototypic pro- anti-inflammatory cytokines IFNγ IL-10 using rhesus macaque model mild COVID-19. We find that drives development 18fluorodeoxyglucose (FDG)-avid lesions in lungs as measured by PET/CT imaging but not required for suppression viral replication. In contrast, limits duration acute lesions, serum markers inflammation magnitude...
To identify and explain morphologic changes of the extraocular muscles (EOMs) in anophthalmic patients.
HIV/Mycobacterium tuberculosis (Mtb) co-infected individuals have an increased risk of prior to loss peripheral CD4 T cells, raising the possibility that HIV co-infection leads cell depletion in lung tissue before it is evident blood. Here, we use rhesus macaques study early effects simian immunodeficiency virus (SIV) on pulmonary granulomas. Two weeks after SIV inoculation Mtb-infected macaques, Mtb-specific cells are dramatically depleted from granulomas, blood, airways, and lymph nodes,...
Viral co-infections have been implicated in worsening tuberculosis (TB) and during the COVID-19 pandemic, global rate of TB-related deaths has increased for first time over a decade. We others previously shown that resolved prior or concurrent influenza A virus infection
Specific proteolytic destruction of the human chemotaxin, C5a, is a property group A and B streptococcal pathogens. Here we show that virulent G streptococci from sources also express C5a peptidase activity. The enzyme responsible for this activity approximately same size as antigenically similar to produced by streptococci. On basis Southern hybridization analysis with an internal fragment gene (scpA) probe, copy was found in genome all isolates tested. Comparison partial restriction maps...
Abstract Programmed death-1 (PD-1) promotes T cell tolerance. Despite therapeutically targeting this pathway for chronic infections and tumors, little is known about how different subsets are affected during blockade. We examined PD-1/PD ligand 1 (PD-L1) regulation of self-antigen–specific CD4 CD8 cells in autoimmune-susceptible models. PD-L1 blockade increased insulin-specific effector type diabetes. However, anergic islet-specific were resistant to Additionally, was critical induction, but...
Abstract Immunization via the respiratory route is predicted to increase effectiveness of a SARS-CoV-2 vaccine. Here, we evaluate immunogenicity and protective efficacy one or two doses live-attenuated murine pneumonia virus vector expressing prefusion-stabilized spike protein (MPV/S-2P), delivered intranasally/intratracheally male rhesus macaques. A single dose MPV/S-2P highly immunogenic, second increases magnitude breadth mucosal systemic anti-S antibody responses levels dimeric IgA in...
Patients with leukocyte adhesion molecule (CDll/ CD18,/32 integrins) deficiency have structural defects in the common /3 subunit (CDls), which prevent heterodimer formation and normal cell surface expression of these receptors, leading to life-threatening bacterial infections.To elucidate nature a patient partial (type 11) deficiency, abnormal CDl8 cDNA clones were isolated, using polymerase chain reaction amplify patient's B cell-derived cDNAs.Sequence analysis revealed two mutant...
More than 85 per cent of the leukocytes are removed from blood by dextran or Plasmagel sedimentation and both high low glycerol freeze‐thaw technics. Larger numbers white cells platelets remain in bloods processed inverted centrifugation, saline washing, agglomeration without freezing. Cytoglomeration is least efficient method removing HL‐A antigens frozen blood. Units prepared this other freezing methods contain nonviable which may not be antigenic.
Abstract Developing vaccine strategies to generate high numbers of Ag-specific CD8 T cells may be necessary for protection against recalcitrant pathogens. Heterologous prime-boost-boost immunization has been shown result in large quantities functional memory with protective capacities and long-term stability. Completing the serial steps heterologous can lengthy, leaving host vulnerable an extensive period time during vaccination process. We show this study that shortening intervals between...
The immune system adapts to constitutive antigens preserve self-tolerance, which is a major barrier for anti-tumor immunity. Antigen-specific reversal of tolerance constitutes goal spur therapeutic applications. Here, we show that robust, iterative, systemic stimulation targeting tissue-specific in the context acute infections reverses established CD8+ T cell self, including cells survive negative selection. This strategy results large numbers circulating and resident memory self-specific...
Control of Mycobacterium tuberculosis (Mtb) infection requires generation T cells that migrate to granulomas, complex immune structures surrounding sites bacterial replication. Here we compared the gene expression profiles in pulmonary bronchoalveolar lavage, and blood Mtb-infected rhesus macaques identify granuloma-enriched cell genes. TNFRSF8/CD30 was among top genes upregulated both CD4 CD8 from granulomas. In mice, CD30 on is required for survival Mtb infection, there no major role...
Between May 2011 and June 2013, we collected the carcasses gastrointestinal tracts of 40 American black bears (Ursus americanus Pallas, 1780) 13 grizzly arctos L., 1758) from populations Alberta British Columbia, Canada. Specimens were examined for helminths, which identified to species level by applying an integrated morphological molecular approach. Our goal was investigate parasite biodiversity infection parameters in sampled bears. We found seven taxa: Dirofilaria ursi Yamaguti, 1941,...
Established T cell dysfunction is a barrier to antitumor responses, and checkpoint blockade presumably reverses this. Many patients fail respond treatment and/or develop autoimmune adverse events. The underlying reason for responsiveness remains elusive. Here, we show that susceptibility dependent on the activation status of cells. Newly activated self-specific CD8 cells cause autoimmunity, which mitigated by inhibiting mechanistic target rapamycin. However, once tolerance established,...
ABSTRACT The envelopment of the Sindbis virus nucleocapsid in modified cell plasma membrane involves a highly specific interaction between capsid (C) protein and endodomain E2 glycoprotein. We have previously identified domain C involved binding to (H. Lee D. T. Brown, Virology 202:390–400, 1994). C-E2 resides hydrophobic cleft with Y180 W247 on opposing sides cleft. Structural modeling studies indicate that domain, which is proposed bind (E2 398T, 399P, 400Y), located at sufficient distance...
ABSTRACT The pro- and anti-inflammatory pathways that determine the balance of inflammation viral control during SARS-CoV-2 infection are not well understood. Here we examine roles IFNγ IL-10 in regulating inflammation, immune cell responses replication rhesus macaques. blockade tended to decrease lung based on 18 FDG-PET/CT imaging but had no major impact innate lymphocytes, neutralizing antibodies, or antigen-specific T cells. In contrast, transiently increased enhanced accumulation...
ABSTRACT SARS-CoV-2 infects via the respiratory tract, but COVID-19 includes an array of non-respiratory symptoms, among them gastrointestinal (GI) manifestations such as vomiting and diarrhea. Here we investigated GI pathology infections in rhesus macaques humans. Macaques experienced mild infection with USA-WA1/2020 shed viral RNA tract stool, including subgenomic indicative replication tract. Intestinal immune cell populations were disturbed, significantly fewer proliferating (Ki67+)...