A5039559366- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Herpesvirus Infections and Treatments
- Cytomegalovirus and herpesvirus research
- Immune Response and Inflammation
- Viral Infections and Vectors
- Inflammasome and immune disorders
- CAR-T cell therapy research
- Cervical Cancer and HPV Research
- HIV Research and Treatment
- interferon and immune responses
- Vaccine Coverage and Hesitancy
- Neuroinflammation and Neurodegeneration Mechanisms
- Virology and Viral Diseases
- Cancer Immunotherapy and Biomarkers
- Reproductive tract infections research
- Monoclonal and Polyclonal Antibodies Research
- Immunodeficiency and Autoimmune Disorders
- Ethics in Clinical Research
- SARS-CoV-2 detection and testing
- Parasites and Host Interactions
- Hepatitis B Virus Studies
- Virus-based gene therapy research
- Reproductive System and Pregnancy
Gates Foundation
2023-2024
Washington University in St. Louis
2017-2023
Office of Infectious Diseases
2020
Yale University
2011-2016
University of Pennsylvania
2008-2014
Howard Hughes Medical Institute
2013
The Wistar Institute
2007-2010
UPMC Hillman Cancer Center
2008
Cancer Research Institute
2008
Johns Hopkins University
1985
Programmed death-1 (PD-1) regulates T cell exhaustion during chronic infections. Blocking the PD-1:PD-ligand (PD-L) pathway reinvigorates exhausted CD8 cells. Exactly how blocking PD-1:PD-L interactions improves immunity, however, remains unclear. blockade could reprogram all cells to become antiviral effectors. Alternatively, this might selectively expand a subset of We have identified two subpopulations viral infection in mice. One is rescued by αPD-L1 blockade, whereas other appears more...
When intracellular pathogens invade mammalian hosts, naïve CD8 + T cells differentiate into cytotoxic killers, which lyse infected target and secrete cytokines that activate microbicides. We show deficient in the transcription factors T-bet eomesodermin (Eomes) fail to functional killers required for defense against lymphocytic choriomeningitis virus. Instead, virus-specific lacking both Eomes an interleukin-17–secreting lineage, reminiscent of helper cell fate has been implicated...
Efficient maintenance of memory CD8 T cells is central to long-term protective immunity. IL-7– and IL-15–driven homeostatic proliferation essential for cell persistence after acute infections. During chronic infections, however, virus-specific respond poorly these cytokines. Yet, often persist long periods time during We have addressed this apparent paradox by examining the mechanism maintaining infection. find that cytokines (e.g., IL-7/15), inflammatory signals, priming recent thymic...
The PD-1/PD-L pathway plays a major role in regulating T-cell exhaustion during chronic viral infections animal models, as well humans, and blockade of this can revive exhausted CD8(+) T cells. We examined the expression PD-1 its ligands, PD-L1 PD-L2, multiple tissues course infection determined how amount expressed, anatomical location, influenced function CD8 on cells from different locations did not always correlate with infectious virus but reflect antigen some tissues. Moreover, lower...
Tissue-resident memory CD8+ T (CD8 TRM) cells are an essential component of protective immune responses at barrier tissues, including the female genital tract. However, mechanisms that lead to initiation CD8 TRM-mediated immunity after viral infection unclear. Here we report TRM established by 'prime and pull' method confer protection against HSV-2 infection, IFN-γ produced is required for this protection. Furthermore, find TRM-cell restimulation depends on a population CD301b+...
Endogenous pyrogen (EP) and interleukin (IL 1) appear to be closely related or identical. We therefore conducted experiments test whether the central action of EP (fever) enhanced its local (potentiation immune responses). found that 3H-TdR incorporation by thymocytes stimulated with IL 1 in presence 5 micrograms/ml phytohemagglutinin (PHA) was strongly small rises temperature 32 38 degrees C range. Responses at 40 were generally less than those seen C. Calculated values for coefficient...
Zika virus (ZIKV), which can cause devastating disease in fetuses of infected pregnant women, be transmitted by mosquito inoculation and sexual routes. Little is known about immune protection against sexually ZIKV. In this study, we show that previous infection through intravaginal or subcutaneous routes with a contemporary Brazilian strain ZIKV protect subsequent challenge homologous strain. Both induced high titers ZIKV-specific neutralizing antibody serum the vaginal lumen. Virus-specific...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of disease 2019 (COVID-19) pandemic, is continuing to cause immense and social economic disruptions. Conventional assays that monitor SARS-CoV-2 growth in cell culture rely on costly time-consuming RNA extraction procedures, hampering progress basic research development effective therapeutics. Here, we developed a simple quantitative real-time PCR assay supernatants does not necessitate as accurate sensitive...
In this report, we describe an experimental strategy for analyzing the interaction of nominal antigen with antigen-specific T cell clones. Our approach was based on notion that low affinity interactions between and receptors might be detected by using a highly multivalent form in which large number identical, appropriately spaced epitopes are attached to polymer backbone. Antigens kind should capable binding cell, resulting marked enhancement overall avidity interaction. To examine...
Type III interferons are potent antiviral cytokines important for regulation of viruses that infect at mucosal surfaces. Studies using mice lacking the Ifnlr1 gene encoding type interferon receptor have demonstrated signaling through this is critical protection against influenza virus, norovirus, and reovirus. Using a genetic approach to disrupt murine cytokine genes Ifnl2 Ifnl3 , we found these fully recapitulate impaired control observed in . Our results support idea an exclusive role...
Neutrophil responses against pathogens must be balanced between protection and immunopathology. Factors that determine these outcomes are not well-understood. In a mouse model of genital herpes simplex virus-2 (HSV-2) infection, which results in severe inflammation, antibody-mediated neutrophil depletion reduced disease. Comparative single-cell RNA-sequencing analysis vaginal cells HSV-1 mild demonstrated sustained expression interferon-stimulated genes (ISGs) only after HSV-2 infection...
Genital herpes is characterized by recurrent episodes of epithelial blistering. The mechanisms causing this pathology are ill defined. Using a mouse model vaginal simplex virus 2 (HSV-2) infection, we show that interleukin-18 (IL-18) acts upon natural killer (NK) cells to promote accumulation the serine protease granzyme B in vagina, coinciding with ulceration. Genetic loss or therapeutic inhibition specific inhibitor reduces disease and restores integrity without altering viral control....
Escherichia coli infection of the female reproductive tract is a significant cause disease in humans and animals, but simple animal models are lacking. Here we report that vaginal inoculation uropathogenic E. strains UTI89 CFT073 non-pregnant, estrogen-treated mice resulted robust colonization vagina uterine horns, whereas titers lab strain MG1655 were significantly lower. Non-estrogenized also became colonized, there was more variation titers. A dose 104 colony-forming units (CFU)...
Herpes simplex virus-2 (HSV-2) and HSV-1 both can cause genital herpes, a chronic infection that establishes latent reservoir in the nervous system. Clinically, recurrence frequency of herpes is considerably less than HSV-2 which correlates with reduced neuronal infection. The factors dictating disparate outcomes are unclear. In this study, we show vaginal mice leads to rapid appearance mature DCs draining lymph node, dependent on an early burst NK cell-mediated IFN-γ production vagina...
Cervical cancer is a major cause of morbidity and mortality globally with disproportionate impact on women in low- middle-income countries. In 2021, the World Health Organization (WHO) called for increased vaccination, screening, treatment to eliminate cervical cancer. However, even widespread rollout human papillomavirus (HPV) prophylactic vaccines, millions who previously acquired HPV infections will remain at risk progression decades come. The development licensing an affordable,...