A5074581391- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Immune Cell Function and Interaction
- Tuberculosis Research and Epidemiology
- T-cell and B-cell Immunology
- Mycobacterium research and diagnosis
- Immunodeficiency and Autoimmune Disorders
- Immunotherapy and Immune Responses
- Parasites and Host Interactions
- Influenza Virus Research Studies
- Immune responses and vaccinations
- Synthesis and Biological Evaluation
- Toxin Mechanisms and Immunotoxins
- Immune Response and Inflammation
- Computational Drug Discovery Methods
- Malaria Research and Control
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- interferon and immune responses
- HIV Research and Treatment
- Parasitic Infections and Diagnostics
- Monoclonal and Polyclonal Antibodies Research
- Respiratory viral infections research
- Helminth infection and control
- vaccines and immunoinformatics approaches
Saint Louis University
2014-2024
Saint Louis University
2016-2023
University Medical Center
2010-2016
National Institute of Allergy and Infectious Diseases
2015
Saint Louis Zoo
2015
UCLouvain Saint-Louis Brussels
1997-2015
Geriatric Research Education and Clinical Center
1996-1997
St. Louis VA Medical Center
1996
Deaconess Hospital
1996
Mucosa-associated invariant T (MAIT) cells are a unique population of αβ in mammals that reside preferentially mucosal tissues and express an Vα paired with limited Vβ T-cell receptor (TCR) chains. Furthermore, MAIT cell development is dependent upon the expression evolutionarily conserved major histocompatibility complex (MHC) class Ib molecule MR1. Using vitro assays, recent studies have shown mouse human activated by antigen-presenting (APCs) infected diverse microbes, including numerous...
Fundamentally understanding the suppressive mechanisms used by different subsets of tumor-infiltrating regulatory T (Treg) cells is critical for development effective strategies antitumor immunotherapy. γδ Treg have recently been identified in human diseases including cancer. However, and functional regulations this new subset unconventional are largely unknown. In current studies, we explored mechanism(s) breast tumor-derived on innate adaptive immunity. We found that induced...
Mucosal-associated invariant T (MAIT) cells have a semi-invariant TCR Vα-chain, and their optimal development is dependent upon commensal flora expression of the nonpolymorphic MHC class I-like molecule MR1. MAIT are activated in an MR1-restricted manner by diverse strains bacteria yeast, suggesting widely shared Ag. Recently, human mouse MR1 were found to bind bacterial riboflavin metabolites (ribityllumazine [RL] Ags) capable activating cells. In this study, we used MR1/RL tetramers study...
Human γ9δ2 T cells potently inhibit pathogenic microbes, including intracellular mycobacteria, but the key inhibitory mechanism(s) involved have not been identified. We report a novel mechanism involving inhibition of mycobacteria by soluble granzyme A. produced factors that could pass through 0.45 µm membranes and in human monocytes cultured below transwell inserts. Neutralization TNF-α co-cultures infected prevented inhibition, suggesting was critical factor cells. However, only siRNA-...
Th17 cells are a subset of CD4+ T known to play central role in the pathogenesis many autoimmune diseases, as well defense against some extracellular bacteria and fungi. However, not believed have significant function intracellular infections. In contrast this paradigm, we discovered that provide robust protection Trypanosoma cruzi, protozoan parasite causes Chagas disease. confer significantly stronger T. cruzi-related mortality than even Th1 cells, traditionally thought be cell most...
Abstract The Trypanosoma cruzi trans-sialidase (TS) is a unique enzyme with neuraminidase and sialic acid transfer activities important for parasite infectivity. T. genome contains large family of TS homologous genes, it has been suggested that homologues provide mechanism immune escape chronic infection. We have investigated whether the consensus enzymatic domain could induce immunity protective against acute chronic, as well mucosal systemic, shown that: 1) TS-specific can protect...
Pulmonary non-tuberculous mycobacterial (NTM) infections particularly caused by Mycobacterium avium complex (MAC) and abscessus (MAB) are becoming major health problems in the U.S. New therapies or vaccines which will help prevent disease, shorten treatment duration and/or increase success rates urgently needed. This study was conducted with objective of testing hypothesis that Bacillus Calmette Guerin (BCG), a vaccine used for prevention serious forms tuberculosis (TB) children adolescents...
In general, gamma interferon (IFN-gamma)-producing CD4(+) Th1 cells are important for the immunological control of intracellular pathogens. We previously demonstrated an association between parasite-specific induction IFN-gamma responses and resistance to protozoan Trypanosoma cruzi. To investigate a potential causal relationship T. cruzi resistance, we studied ability protect susceptible BALB/c mice against virulent parasite challenges. developed immunization protocols capable inducing...
Cruzipain, the major cysteinyl proteinase of Trypanosoma cruzi, is expressed by all developmental forms and strains parasite stimulates potent humoral cellular immune responses during infection in both humans mice. This information suggested that cruzipain could be used to develop an effective T. cruzi vaccine. To study whether cruzipain-specific T cells inhibit intracellular replication, we generated cruzipain-reactive CD4(+) Th1 cell lines. These produced large amounts gamma interferon...
Background Immunization of mice with the Trypanosoma cruzi trans-sialidase (TS) gene using plasmid DNA, adenoviral vector, and CpG-adjuvanted protein delivery has proven highly immunogenic provides protection against acute lethal challenge. However, long-term induced by TS DNA vaccines not been reported. The goal present work was to test whether co-administration a encoding IL-15 (pIL-15) could improve duration achieved through genetic vaccination (pTS) alone. Methodology We immunized BALB/c...
Chagas' disease, induced by Trypanosoma cruzi, is a common cause of infectious myocarditis. Recent clinical treatment trials and vaccine studies indicate that chagasic immunopathology directed against the parasite not self-antigens. Therefore, vaccines may have potential to protect disease progression. Certain combinations mouse strains produce significant histopathology can be used for safety analyses new vaccination strategies. The goals this study were determine (1) whether development...
Given the threat of drug resistance, there is an acute need for new classes antimalarial agents that act via a unique mechanism action relative to currently used drugs. We have identified set druglike compounds within Tres Cantos Anti-Malarial Set (TCAMS) which likely inhibition Plasmodium aspartic protease. Structure–activity relationship analysis and optimization these aminohydantoins demonstrate are potent nanomolar inhibitors proteases PM-II PM-IV one or more other proteases....
Vaccines against mucosally invasive, intracellular pathogens must induce a myriad of immune responses to provide optimal mucosal and systemic protection, including CD4(+) T cells, CD8(+) Ab-producing B cells. In general, cells are known important helper functions for both cell responses. However, the relative importance protection is less clearly defined. We have studied these questions in detail using murine model Trypanosoma cruzi infection. Despite our initial hypothesis that Abs would be...
Induction of local antibody responses to influenza A virus hemagglutinin by coadministration two vaccines was investigated. Fifty elderly nursing home residents received inactivated trivalent vaccine intramuscularly and simultaneously were randomized receive either bivalent live attenuated or saline placebo intranasally in a blinded fashion. More significant increases anti-H1 -H3 IgA antibodies detectable nasal wash specimens subjects who than those intranasal placebo. The increased...
ABSTRACT Chagas' disease results from infection with Trypanosoma cruzi , a protozoan parasite that establishes systemic intracellular after mucosal invasion. We hypothesized ideal vaccines for mucosally invasive, pathogens like T. should induce type 2 immunity optimal induction of protective secretory immunoglobulin A (IgA) and 1 against replication. However, differential immune memory could be difficult to because reciprocal inhibitory actions between responses. To test our hypotheses, we...
It has been hypothesized that optimal vaccine immunity against mucosally invasive, intracellular pathogens may require the induction of different types immune responses in mucosal and systemic lymphoid tissues. Mucosal type 2/3 (producing interleukin-4 [IL-4], IL-6 and/or transforming growth factor beta) could be necessary for protective secretory immunoglobulin A responses. On other hand, 1 (including gamma interferon [IFN-gamma], tumor necrosis alpha, cytotoxic T-cell responses) are likely...
Trypanosoma cruzi is an intracellular parasite and the causative agent of Chagas disease. Previous work has shown that chemokine receptor CCR5 plays a role in systemic T. protection. We evaluated importance CCL5 for mucosal protection against natural oral conjunctival challenges. cruzi-immune CCR5(-/-) wild-type C57BL/6 mice were generated by repeated infectious challenges with cruzi. developed equivalent levels cellular, humoral, protective responses. However, CCR5(-/-)-immune produced...
Mycobacterium tuberculosis remains a major global challenge to human health care, and the mechanisms of how M. evades host immune surveillance favor its survival are still largely unknown. In this study, we found that bacillus Calmette-Guérin (BCG) viable as well lysates could activate IL-27 expression in mouse macrophages by induction p28 subunit transcription. However, parallel with these effects, BCG lysate stimulation induced activation p38 MAPK signaling molecules MLK3/MKK3/MK2 prevent...
Trypanosoma cruzi is a protozoan parasite that can initiate mucosal infection after conjunctival exposure. The anatomical route of T. invasion and spread contamination remains poorly characterized. In the present work we have identified sites initial replication contaminative challenges with metacyclic trypomastigotes using combination immunohistochemical real-time PCR confirmatory techniques in 56 mice between 3 14 days challenge. Our results demonstrate predominant involves drainage...
Trypanosoma cruzi is an intracellular protozoan parasite capable of infecting through mucosal surfaces. Our laboratory has previously elucidated the anatomical routes infection after both conjunctival and gastric challenge in mice. We have shown that chronically infected mice develop strong immune responses protecting against subsequent rechallenge with virulent parasites gastric, conjunctival, systemic infection. also intranasal immunizations unique T. trans-sialidase (TS) antigen protect...
ABSTRACT There is a growing interest in repurposing mycobacterial efflux pump inhibitors, such as verapamil, for tuberculosis (TB) treatment. To aid the design of better analogs, we studied effects verapamil on macrophages and Mycobacterium -specific T cells. Macrophage activation was evaluated by measuring levels nitric oxide, tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), gamma interferon (IFN-γ). Since known autophagy inducer, roles induction antimycobacterial activities...
The translationally silent 100S ribosome is a poorly understood form of the dimeric 70S complex that ubiquitously found in all bacterial phyla. elimination hibernating leads to translational derepression, instability, antibiotic sensitivity, and biofilm defects some bacteria. In Firmicutes, such as opportunistic pathogen Staphylococcus aureus, 190-amino acid protein called hibernating-promoting factor (HPF) dimerizes conjoins two ribosomes through direct interaction between HPF homodimer,...