A5001753346- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Phagocytosis and Immune Regulation
- CAR-T cell therapy research
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Viral Infections and Vectors
- Viral Infections and Outbreaks Research
- Immune cells in cancer
- Mosquito-borne diseases and control
- Virology and Viral Diseases
- Poxvirus research and outbreaks
- Virus-based gene therapy research
- Prion Diseases and Protein Misfolding
- Immune responses and vaccinations
- Bacillus and Francisella bacterial research
- Long-Term Effects of COVID-19
- Rabies epidemiology and control
- Vector-Borne Animal Diseases
- T-cell and Retrovirus Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Metal complexes synthesis and properties
- Cell Adhesion Molecules Research
- Retinal and Optic Conditions
National Institute of Allergy and Infectious Diseases
2012-2025
National Institutes of Health
2012-2025
University of North Texas
2014
University of North Texas System
2014
University of North Texas Health Science Center
2014
UConn Health
2003-2006
Oregon State University
2003
Emory University
2003
University of Florida
1990
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...
Although chronic infections with viruses such as HIV and hepatitis C virus have been associated regulatory T cell (Treg)-mediated suppression of virus-specific CD8 + T-cell activity, no causal relationship between Tregs viral set points has established. Using transgenic mice in which can be selectively ablated, we now show that transient depletion during a retroviral infection allows exhausted cells to regain antiviral functions, including secretion cytokines, production cytotoxic molecules,...
Abstract CD40, 4-1BB, and OX40 are costimulatory molecules belonging to the TNF/nerve growth factor superfamily of receptors. We examined whether simultaneous costimulation affected responses T cells using several different in vivo tracking models mice. show that enforced dual through 4-1BB OX40, but not induced profound specific CD8 cell clonal expansion. In contrast, response CD4 was additive rather than synergistic. The synergistic persevered for weeks, expanded effector resided...
Abstract We identified a murine peptide-specific CD8 T regulatory cell population able to suppress responding CD4 cells. Immunization with OVA, poly(I:C), and anti-4-1BB generated of SIINFEKL-specific cells that profoundly inhibited peptide-responding from cellular division. The mechanism suppression required IFN-γ, but IFN-γ alone was not sufficient the data show were unable unless they engaged IFN-γ. Furthermore, even in absence recall peptide, suppressed responses as long present. To...
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,...
It was recently reported that inhibitory molecules such as programmed death-1 (PD-1) were upregulated on CD8(+) T cells during acute Friend retrovirus infection and the prematurely exhausted dysfunctional in vitro. The current study confirms most activated expression of PD-1 revealed a dichotomy function between PD-1(hi) PD-1(lo) subsets. More produced antiviral cytokines IFN-γ TNF-α, whereas more displayed characteristics cytotoxic effectors production granzymes surface CD107a. Importantly,...
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...
Paradoxically, early host responses to infection include the upregulation of antiphagocytic molecule, CD47. This suggests that CD47 blockade could enhance antigen presentation and subsequent immune responses. Indeed, mice treated with anti-CD47 monoclonal antibody following lymphocytic choriomeningitis virus infections show increased activation both macrophages dendritic cells (DCs), enhancement kinetics potency CD8+ T cell responses, significantly improved control. Treatment efficacy is...
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...
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...
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,...
To better understand how innate and adaptive immune responses interact with each other, we combined 4-1BB T cell costimulation specific adjuvants to determine whether these treatments would influence expansion function in vivo . In the presence of ligation Toll-like receptor 3 (TLR)3 and/or TLR4 triggering, CD8 clonal survival was augmented profoundly. Specific cells primed TLR ligands responded normally vitro recall stimulus, but, surprisingly, copriming significantly impaired response even...
Abstract Vβ5+ regulatory T cells (Tregs), which are specific for a mouse endogenous retroviral superantigen, become activated and proliferate in response to Friend virus (FV) infection. We previously reported that FV-induced expansion of this Treg subset was dependent on CD8+ TNF-α, but independent IL-2. now show the inflammatory milieu associated with FV infection is not necessary induction expansion. Rather, it presence critical their The data indicate mechanism involves signaling between...
Abstract The most recent Sudan virus (SUDV) outbreak in Uganda was first detected September 2022 and resulted 164 laboratory-confirmed cases 77 deaths. There are no approved vaccines against SUDV. Here, we investigated the protective efficacy of ChAdOx1-biEBOV cynomolgus macaques using a prime or prime-boost regimen. is replication-deficient simian adenovirus vector encoding SUDV Ebola (EBOV) glycoproteins (GPs). Intramuscular vaccination induced EBOV GP-specific immunoglobulin G responses...
In practice, vaccines should induce lasting and efficacious T cell immunity without promoting deleterious pathological consequences. To accomplish this goal we immunized mice with ovalbumin peptide, polyinosinic–polycytidylic anti-CD137. Vaccinated retained a massive functional CD8 memory pool in lymphoid non-lymphoid tissues for >1 year. The cells clonally expanded, produced substantial amounts of IFNγ, responded vigorously to vesicular stomatitis virus infection. understand how the vaccine...
Abstract Friend virus infection of mice induces the expansion and activation regulatory T cells (Tregs) that dampen acute immune responses promote establishment maintenance chronic infection. Adoptive transfer experiments expression neuropilin-1 indicate these are predominantly natural Tregs rather than virus-specific conventional CD4+ converted into induced Tregs. Analysis Treg TCR Vβ chain usage revealed a broadly distributed polyclonal response with high proportionate Vβ5+ subset, which...
La Crosse Virus (LACV) is a primary cause of pediatric viral encephalitis in the USA and can result severe clinical outcomes. Almost all cases LACV occur children 16 years or younger, indicating an age-related susceptibility. This susceptibility recapitulated mouse model where weanling (3 weeks old younger) mice are susceptible to LACV-induced disease, adults (greater than 6 weeks) resistant. Disease humans associated with infiltrating leukocytes CNS. However, what cell types into brain...
Infection of mice with Friend virus induces the activation CD4(+) regulatory T cells (Tregs) that suppress virus-specific CD8(+) cells. This suppression leads to incomplete clearance and establishment persistence. We now show Treg-mediated is tissue specific, occurring in spleen but not liver. Regardless infection status, there was a 5-fold lower proportion Tregs liver than spleen, much absolute cell numbers, relatively few present expressed less CD25. Results indicated reduced expression...
Abstract In general, TGFβ is synthesized as a procytokine that requires proteolytic activation, release of the mature cytokine from its noncovalently associated latent-associated peptide, and binding to TGFβRII mediate suppressive activity. We tracked this process in mice containing primed CD8 regulatory T cells (Tregs) by immunoblotting primary whole cell lysates for pro-TGFβ, peptide TGFβ. Generation Tregs promoted processing 50 kDa pro-TGFβ protein into 12.5 species vivo. Despite...
Published data show that murine bone marrow-derived macrophages (BMDM) restrict growth of avirulent phase II, but not virulent I, Coxiella burnetii. Growth restriction II bacteria is thought to result from potentiated recognition pathogen-associated molecular patterns, which leads production inhibitory effector molecules. Past studies have used conditioned medium L-929 fibroblasts as a source macrophage-colony stimulating factor (M-CSF) promote differentiation myeloid precursors into...