A5078243832- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Tuberculosis Research and Epidemiology
- HIV Research and Treatment
- Mycobacterium research and diagnosis
- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- Cytokine Signaling Pathways and Interactions
- Immunodeficiency and Autoimmune Disorders
- Force Microscopy Techniques and Applications
- Advanced Biosensing Techniques and Applications
- RNA Interference and Gene Delivery
- Psoriasis: Treatment and Pathogenesis
- CAR-T cell therapy research
- Advanced biosensing and bioanalysis techniques
- interferon and immune responses
- Viral Infections and Immunology Research
- Circular RNAs in diseases
- Cell Adhesion Molecules Research
- RNA modifications and cancer
- Lipid Membrane Structure and Behavior
- Pneumocystis jirovecii pneumonia detection and treatment
- Virus-based gene therapy research
- vaccines and immunoinformatics approaches
- Advanced Electron Microscopy Techniques and Applications
University of Illinois Urbana-Champaign
2012-2022
University of Illinois Chicago
2013-2022
Illinois College
2012-2022
Institut Pasteur of Shanghai
2014-2016
Chinese Academy of Sciences
2015
Beth Israel Deaconess Medical Center
1998-2004
Harvard University
1993-2004
Novosibirsk Tuberculosis Research Institute
2002-2003
Beth Israel Deaconess Hospital
2003
Oklahoma State University
1999
The role of CD8 T cells in anti-tuberculosis immunity humans remains unknown, and studies cell–mediated protection against tuberculosis mice have yielded controversial results. Unlike mice, nonhuman primates share a number important features the immune system that relate directly to specificity functions cells, such as expression group 1 CD1 proteins are capable presenting Mycobacterium lipids antigens cytotoxic/bactericidal protein granulysin. Employing more relevant primate model human...
To examine the role of T cell receptor (TCR) in γδ cells adaptive immunity, a macaque model was used to follow Vγ2Vδ2 + responses mycobacterial infections. These phosphoantigen-specific displayed major expansion during Mycobacterium bovis Bacille Calmette-Guérin (BCG) infection and clear memory-type response after BCG reinfection. Primary recall expansions were also seen tuberculosis naı̈ve BCG-vaccinated macaques, respectively. This capacity rapidly expand coincided with clearance...
Molecular mechanisms for T-cell immune responses modulated by T cell-inhibitory molecules during tuberculosis (TB) infection remain unclear. Here, we show that active human TB up-regulates CD244 and signaling-associated in CD8(+) cells blockade of signaling enhances production IFN-γ TNF-α. expression/signaling correlates with high levels a long noncoding RNA (lncRNA)-BC050410 [named as lncRNA-AS-GSTT1(1-72) or lncRNA-CD244] the CD244(+)CD8(+) subpopulation. drives lncRNA-CD244 expression via...
Abstract Ursolic acid (UA) has proved to have broad-spectrum anti-tumor effects, but its poor water solubility and incompetent targeting property largely limit clinical application efficiency. Here, we synthesized a nanoparticle-based drug carrier composed of chitosan, UA folate (FA-CS-UA-NPs) demonstrated that FA-CS-UA-NPs could effectively diminish off-target effects increase local concentrations UA. Using MCF-7 cells as in vitro model for anti-cancer mechanistic studies, found be easily...
Filoviruses, consisting of Ebola virus (EBOV) and Marburg (MARV), are among the most lethal infectious threats to mankind. Infections by these viruses can cause severe hemorrhagic fevers in humans nonhuman primates with high mortality rates. Since there is currently no vaccine or antiviral therapy approved for humans, an urgent need develop prophylactic therapeutic options use during filoviral outbreaks bioterrorist attacks. One ideal targets against infection diseases at entry step, which...
Dominant Vγ2Vδ2 T-cell subset exist only in primates, and recognize phosphoantigen from selected pathogens including M. tuberculosis(Mtb). In vivo function of T cells tuberculosis remains unknown. We conducted mechanistic studies to determine whether earlier expansion/differentiation during Mtb infection could increase immune resistance macaques. Phosphoantigen/IL-2 administration specifically induced major expansion pulmonary trafficking/accumulation phosphoantigen-specific cells,...
Significance Despite the urgent need for a better tuberculosis (TB) vaccine, relevant protective mechanisms remain unknown. We previously defined phosphoantigen (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP)–specific Vγ2Vδ2 T cells as unique subset in primates, and, here, we immunized them selectively protection against TB. A single respiratory vaccination of macaques with attenuated HMBPP-producing Listeria monocytogenes (Lm ΔactA prfA *), but not an HMBPP-lacking ΔgcpE strain,...
Abstract Pathogenesis hallmarks for tuberculosis (TB) are the Mycobacterium (Mtb) escape from phagolysosomal destruction and limited drug delivery into infected cells. Several nanomaterials can be entrapped in lysosomes, but development of functional to promote Mtb clearance remains a big challenge. Here, we report on bactericidal effects selenium nanoparticles (Se NPs) against further introduce novel nanomaterial‐assisted anti‐TB strategy manipulating Ison@Man‐Se NPs synergistic...
T-cell immune responses modulated by immunoglobulin and mucin domain-containing molecule 3 (Tim-3) during Mycobacterium tuberculosis (Mtb) infection in humans remain poorly understood. Here, we found that active TB patients exhibited increases numbers of Tim-3-expressing CD4+ CD8+ T cells, which preferentially displayed polarized effector memory phenotypes. Consistent with phenotypes, Tim-3+CD4+ Tim-3+CD8+ subsets showed greater functions for producing Th1/Th22 cytokines CTL molecules than...
Selenium nanoparticles (Se NPs) have attracted increasing interest in recent decades because of their anticancer, immunoregulation, and drug carrier functions. In this study, GE11 peptide-conjugated Se NPs (GE11-Se NPs), a nanosystem targeting EGFR over-expressed cancer cells, were synthesized for oridonin delivery to achieve enhanced anticancer efficacy. Oridonin loaded peptide conjugated (GE11-Ori-Se found show cellular uptake which resulted inhibition against cells reduced toxicity normal...
The possibility that CD4(+) T cells can act as "innate-like" to contain very early Mycobacterium tuberculosis dissemination and function master helpers sustain multiple effector functions of CD8(+) CD3(-) lymphocytes during development adaptive immunity against primary (TB) has not been demonstrated. We showed pulmonary M. infection CD4-depleted macaques surprisingly led extrapulmonary dissemination, whereas CD4 deficiency clearly resulted in rapid TB progression. depletion revealed the...
Abstract The possibility that simultaneous expansion of T regulatory cells (Treg) and effector early postinfection can confer some immunological benefits has not been studied. In this study, we tested the hypothesis early, cytokine Treg in a tissue infection site allow these cell populations to act concert control inflammation/damage while containing infection. IL-2 treatments after Mycobacterium tuberculosis macaques induced CD4+CD25+Foxp3+ Treg, CD8+CD25+Foxp3+ cells, CD4+ effector/CD8+...
Abstract The dominant Vγ2Vδ2 T cell subset recognizes phosphoantigen and exists only in humans nonhuman primates. Despite the discovery of γδ cells >30 y ago, a proof-of-concept study has not been done to prove principle that is protective against Mycobacterium tuberculosis other infections. In this study, we used an adoptive cell–transfer strategy define role primate (TB) model. for transfer displayed central/effector memory mounted effector functions, including production anti–M....
Evidence indicates that cytotoxic T lymphocytes (CTLs) may be important in containing the spread of human immunodeficiency virus (HIV) infected host. Although use recombinant viruses has been proposed as an approach to elicit protective immunity against HIV, ability viral constructs CD8+ CTL responses higher primates never demonstrated. A live virus, vaccinia-simian macaques (SIVmac), was used determine whether such a genetically restricted, lymphocyte-mediated antiviral response could...
The immune mechanisms by which early host-mycobacterium interaction leads to the development of severe tuberculosis (TB) remain poorly characterized in humans. Here, we demonstrate that TB juvenile rhesus monkeys down-regulated many genes blood but up-regulated selected constituting gene networks Th17 and Th1 responses, T cell activation migration, inflammation chemoattractants pulmonary lymphoid compartments. Overexpression (450–2740-fold) 13 encoding inflammatory cytokines receptors...
Although microbial (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) can activate primate Vgamma2Vdelta2 T cells, molecular mechanisms by which HMBPP interacts with cells remain poorly characterized. Here, we developed soluble, tetrameric TCR of rhesus macaques to define HMBPP/APC interaction TCR. While exogenous was associated APC membrane in an appreciable affinity, the membrane-associated readily bound tetramer. The tetramer shown bind stably presented on various cell lines from...
Abstract Although phosphoantigen-specific Vγ2Vδ2 T cells appear to play a role in antimicrobial and anticancer immunity, mucosal immune responses effector functions of these γδ during infection or phospholigand treatment remain poorly characterized. In this study, we demonstrate that the microbial phosphoantigen (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) plus IL-2 macaques induced prolonged major expansion circulating expressed CD8 produced cytotoxic perforin their peak...