A5055428999- Immune Cell Function and Interaction
- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Infectious Diseases and Tuberculosis
- Cancer Immunotherapy and Biomarkers
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Immunodeficiency and Autoimmune Disorders
- CAR-T cell therapy research
- Long-Term Effects of COVID-19
- Cytomegalovirus and herpesvirus research
- Fungal Infections and Studies
- HIV Research and Treatment
- Cytokine Signaling Pathways and Interactions
- Immune responses and vaccinations
- Pericarditis and Cardiac Tamponade
- Animal health and immunology
- Antimicrobial Peptides and Activities
- Respiratory viral infections research
- Antifungal resistance and susceptibility
- Diagnosis and treatment of tuberculosis
- Asthma and respiratory diseases
National Institutes of Health
2016-2025
National Institute of Allergy and Infectious Diseases
2016-2025
Universidad San Pablo CEU
2022
Center for Independent Living
2020
Information Today (United States)
2020
Emory University
2004-2017
Jiangsu Institute of Parasitic Diseases
2010-2017
Endocyte (United States)
2012
University of Minnesota Medical Center
2009
University of Minnesota
2009
Immunotherapeutic PD-1–targeted therapies require CD28 to promote cancer cell killing.
Migration to intestinal mucosa putatively depends on local activation because gastrointestinal lymphoid tissue induces expression of homing molecules, whereas skin-draining lymph nodes do not. This paradigm is difficult reconcile with reports T cell responses after alternative routes immunization. We this discrepancy by demonstrating that within spleen results in intermediate induction potential the mucosa. further demonstrate memory cells small intestine epithelium not routinely recirculate...
Memory T cells can persist for extended periods in the absence of antigen, and long-term cell immunity is often seen after acute infections. Paradoxically, there have been observations suggesting that memory may be antigen-dependent during chronic To elucidate underlying mechanisms we compared CD8 differentiation an versus infection by using mouse model with lymphocytic choriomeningitis virus. We found a virus-specific failed to acquire cardinal property antigen-independent persistence....
To investigate the respective contributions of TLR versus IL-1R mediated signals in MyD88 dependent control Mycobacterium tuberculosis, we compared outcome M. tuberculosis infection MyD88, TRIF/MyD88, IL-1R1, and IL-1beta-deficient mice. All four strains displayed acute mortality with highly increased pulmonary bacterial burden suggesting a major role for IL-1beta signaling determining phenotype. Unexpectedly, infected TRIF/MyD88-deficient mice, rather than being defective expression,...
Abstract In this study, we examined the cytotoxic activity of effector and memory CD8 T cells in vivo. At peak CTL response following an acute lymphocytic choriomeningitis virus infection, exhibited extremely rapid killing started to eliminate adoptively transferred target within 15 min by a perforin-dependent mechanism. Although resting are poorly cytolytic vitro 51Cr release assays, there was elimination (within 1–4 h) after transfer into immune mice, both CD62Lhigh CD62Llow were able kill...
Whether tissue microenvironment influences memory CD8 T cell differentiation is unclear. We demonstrate that virus-specific intraepithelial lymphocytes in gut resemble neither central nor effector cells isolated from spleen or blood. This unique phenotype arises situ within the gut, suggesting anatomic location plays an inductive role program. In support of this hypothesis, changed upon change location. After transfer and vivo restimulation, proliferated, disseminated into adopted...
IFN-γ-producing CD4 T cells are required for protection against Mycobacterium tuberculosis (Mtb) infection, but the extent to which IFN-γ contributes overall cell-mediated remains unclear. Furthermore, it is not known if increasing production by desirable in Mtb infection. Here we show that accounts only ~30% of cell-dependent cumulative bacterial control lungs over first six weeks >80% spleen. Moreover, capacity ~2 fold exacerbates lung infection and leads early death host, despite...
Although CD4 T cells are required for host resistance to Mycobacterium tuberculosis, they may also contribute pathology. In this study, we examine the role of inhibitory receptor PD-1 and its ligand PD-L1 during M. tuberculosis infection. After aerosol exposure, knockout (KO) mice develop high numbers tuberculosis-specific but display markedly increased susceptibility Importantly, show that themselves drive bacterial loads pathology seen in infected KO mice, deficiency is sufficient trigger...
Abstract Th1 cells are critical for containment of Mycobacterium tuberculosis infection, but little else is known about the properties protective CD4 T cell responses. In this study, we show that pulmonary response against M. composed two populations either CXCR3hi and localize to lung parenchyma or CX3CR1hiKLRG1hi retained within blood vasculature. tuberculosis–specific parenchymal migrate rapidly back into upon adoptive transfer, whereas intravascular effectors produce highest levels IFN-γ...
Increased Mtb-specific T H 1 responses precede tuberculosis associated with PD-1 blockade.
Human monogenic disorders have revealed the critical contribution of type 17 responses in mucosal fungal surveillance. We unexpectedly found that certain settings, enhanced 1 immunity rather than defective can promote infection susceptibility. Notably, mice and humans with
Therapeutic vaccination is a potentially promising strategy to enhance T cell immunity and viral control in chronically infected individuals. However, therapeutic approaches have fallen short of expectations, effective boosting antiviral responses has not always been observed. One the principal reasons for limited success that virus-specific cells become functionally exhausted during chronic infections. We now provide novel enhancing efficacy vaccines. In this study, we show blocking...
Numerous microbes establish persistent infections, accompanied by antigen-specific CD8 T cell activation. Pathogen-specific cells in chronically infected hosts are often phenotypically and functionally variable, as well distinct from responding to nonpersistent infections; this phenotypic heterogeneity has been attributed an ongoing reencounter with antigen. Paradoxically, maintenance of memory acutely resolved infections is antigen independent, whereas there a dependence on for survival...
In the early stages of viral infection, outcomes depend on a race between expansion infection and immune response generated to contain it. We combined in situ tetramer staining with hybridization visualize, map, quantify relationships effector cells their targets tissues. simian immunodeficiency virus infections macaques lymphocytic choriomeningitis mice, magnitude timing establishment an excess versus were found correlate extent control outcome (i.e., clearance partial or poor persistent...
CD4 T cells play a critical role in regulating CD8 T-cell responses during chronic viral infection. Several studies animal models and humans have shown that the absence of help results severe dysfunction virus-specific cells. However, whether function can be restored already exhausted by providing at later time remains unexplored. In this study, we used mouse model lymphocytic choriomeningitis virus (LCMV) infection to address question. Adoptive transfer LCMV-specific into chronically...
Abstract Although adjuvants are critical vaccine components, their modes of action poorly understood. In this study, we investigated the mechanisms by which heat-killed mycobacteria in CFA promote Th17 CD4+ T cell responses. We found that IL-17 secretion cells following immunization requires MyD88 and IL-1β/IL-1R signaling. Through measurement Ag-specific responses after adoptive transfer OTII cells, confirmed MyD88-dependent signaling controls differentiation rather than simply production...
White nose syndrome, caused by Geomyces destructans, has killed more than 5 million cave hibernating bats in eastern North America. During hibernation, the lack of inflammatory cell recruitment at site fungal infection and erosion is consistent with a temperature-induced inhibition immune trafficking. This suppression allows G. destructans to colonize erode skin wings, ears muzzle bat hosts unchecked. Yet, paradoxically, within weeks emergence from hibernation an intense neutrophilic...