A5088544686- Infectious Diseases and Tuberculosis
- Mycobacterium research and diagnosis
- Immune Cell Function and Interaction
- Tuberculosis Research and Epidemiology
- Poxvirus research and outbreaks
- T-cell and B-cell Immunology
- HIV Research and Treatment
- Virus-based gene therapy research
- Immune cells in cancer
- Immune responses and vaccinations
- Pneumocystis jirovecii pneumonia detection and treatment
- Herpesvirus Infections and Treatments
- Immunodeficiency and Autoimmune Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Peripheral Neuropathies and Disorders
- Autoimmune and Inflammatory Disorders
- Nerve injury and regeneration
- Inflammasome and immune disorders
- Neurogenesis and neuroplasticity mechanisms
- vaccines and immunoinformatics approaches
- Diagnosis and treatment of tuberculosis
- Antimicrobial Peptides and Activities
- Autoimmune and Inflammatory Disorders Research
- Viral Infectious Diseases and Gene Expression in Insects
- Orthopedic Infections and Treatments
National Institute of Allergy and Infectious Diseases
2015-2025
National Institutes of Health
2015-2025
Johns Hopkins University
2021
Type Media Center
2020
The management of corticosteroid refractory immune reconstitution inflammatory syndrome (IRIS) is currently unclear. Infliximab administration was associated with clinical improvement without significant adverse events in 3 patients mycobacterial IRIS. Immunologic and virologic responses to antiretroviral therapy were unaffected. Tumor necrosis factor blockade may be beneficial for IRIS warrants further study trials.
Immune reconstitution inflammatory syndrome (IRIS) is an aberrant response in individuals with advanced human immunodeficiency virus (HIV) infection, after antiretroviral therapy (ART) initiation. The pathogenesis of Mycobacterium avium complex (MAC)–associated IRIS has not been fully elucidated. We investigated monocyte and CD4+ T-cell responses vitro, tumor necrosis factor (TNF) expression tissues, plasma cytokines markers, 13 HIV-infected patients MAC-IRIS 14 HIV-uninfected pulmonary MAC...
Abstract Macrophages orchestrate tissue immunity from the initiation and resolution of antimicrobial immune responses to repair damaged tissue. Murine studies demonstrate that tissue-resident macrophages are a heterogenous mixture yolk sac–derived cells populate before birth, bone marrow–derived replacements recruited in adult tissues at steady-state increased numbers response damage or infection. How this translates species constantly under immunologic challenge, such as humans, is unknown....
CD4 expression identifies a subset of mature T cells primarily assisting the germinal center reaction and contributing to CD8+ T-cell B-cell activation, functions, longevity. Herein, we present family in which novel variant disrupting translation-initiation codon gene resulted complete loss membrane plasma soluble peripheral blood, lymph node, bone marrow, skin, ileum homozygous proband. This inherited knockout disease illustrates clinical immunological features deficiency any functional...
Immune reconstitution inflammatory syndrome (IRIS) is an complication associated with underlying opportunistic infection that can be observed in HIV-infected individuals shortly after the initiation of antiretroviral therapy, despite successful suppression HIV viral load and CD4 + T cell recovery. Better understanding IRIS pathogenesis would allow for targeted prevention therapeutic approaches. In this study, we sought to evaluate metabolic perturbations across longitudinal time points using...
Abstract Patients with primary immunodeficiencies undergoing allogeneic hematopoietic cell transplantation (HCT) for difficult-to-control infections can experience immune reconstitution inflammatory syndrome (IRIS) following engraftment. In 3 patients post-HCT IRIS related to mycobacterial infection, in vitro data demonstrate the emergence of pathogen-specific responses and a concomitant rise plasma markers.
Abstract Mycobacterium genavense is a challenging opportunistic pathogen to diagnose and manage in patients with human immunodeficiency virus (HIV). Persistent immunosuppression or protracted immune reconstitution inflammatory syndrome can lead complicated clinical courses. We describe 3 cases of M. HIV representing the spectrum between disease burden strength response.
After recognition of cognate antigen (Ag), effector CD8+ T cells secrete serine proteases called granzymes in conjunction with perforin, allowing to enter and kill target cells. While the roles for some during antiviral immune responses are well characterized, function others, such as granzyme C its human ortholog H, is still unclear. Granzyme constitutively expressed by mature, cytolytic innate lymphoid 1 (ILC1s). Whether other also produce whether it continually or responsive environment...
Abstract Paradoxical inflammatory reactions associated with treatment of neurotuberculosis can lead to severe morbidity and mortality may not be controlled by steroids alone. We report the use Janus kinase inhibitor ruxolitinib treat a steroid-refractory paradoxical reaction.
Abstract Distinguishing disseminated Mycobacterium marinum from multifocal cutaneous disease in persons with human immunodeficiency virus/AIDS can present a diagnostic challenge, especially the context of immune reconstitution inflammatory syndrome (IRIS). In this work, we demonstrate utility flow cytometry and whole genome sequencing (WGS) to diagnose M. unmasked by IRIS following initiation antiretroviral therapy. Flow demonstrated robust cytokine production CD4 T cells response...
The skin is a complex tissue that provides strong physical barrier against invading pathogens. Despite this, many viruses can access the and successfully replicate in either epidermal keratinocytes or dermal immune cells. In this review, we provide an overview of antiviral T cell biology responding to cutaneous viral infections how these responses differ depending on cellular targets infection. Much our mechanistic understanding surveillance infection has been gained from murine models...
ABSTRACT Vaccinia virus (VACV) infection induces prominent changes in host cell metabolism. Little is known about the global metabolic reprogramming that takes place whole tissue during viral infection. Here, we performed a longitudinal metabolomics study VACV-infected mouse skin to investigate We assessed metabolites homogenized of ear pinnae over time presence or absence antigen-specific T cells using untargeted mass spectrometry. VACV induced several significant tissue, including levels...
Low nadir CD4 T-cell counts in HIV + patients are associated with high morbidity and mortality lasting immune dysfunction, even after antiretroviral therapy (ART). The early events of recovery T cells B severely lymphopenic have not been fully characterized. In a cohort (CD4 count < 100/µL) patients, we studied mononuclear isolated from peripheral blood (PB) lymph nodes (LN) pre-ART (n = 40) 6-8 weeks post-ART 30) evaluation cellular immunophenotypes; histology on LN sections;...
Abstract Macrophages are critical orchestrators of tissue immunity, from the initiation and resolution antimicrobial immune responses to subsequent repair damaged tissue. Murine studies have demonstrated that tissue-resident macrophages comprised a mixture yolk sac-derived cells populate before birth hematopoietic-derived replacements recruited in adult tissues both at steady-state increased numbers response damage or infection. While resident some murine readily turned over replaced, other...
Abstract Viral infections induce prominent alterations to the host metabolism. Vaccinia virus (VACV) has been used as a live vaccine preventing smallpox and monkeypox. However, much remains unknown about metabolic regulations of adaptive immune response mounted VACV infection in skin. To survey changes during clearance, we performed longitudinal metabolomics study based on our cutaneous murine model. We adoptively transferred OT-I CD8 +T cells into Rag−/−mice, then infected one ear with...
Abstract Cytotoxic CD8 +T cells are important for the control of many different pathologies in skin, including cutaneous viral infections and skin cancers. One cancer, melanoma, is responsible deaths each year US alone. Despite this, we still have much to learn regarding mechanisms that prevent eliminate Our laboratory has had a long-standing interest better understanding biology T responding poxvirus vaccinia (VACV). To understand global CD8+ cell effector function, also established...
IRIS has been previously described in patients infected with human immunodeficiency virus upon initiation of antiretroviral therapy. We present similar phenomena observed primary immunodeficiencies after alloBMT. Patient 1 is a 59-year old female dominant partial IFNGR1 deficiency and disseminated, treatment refractory MAC. Prior to alloBMT, she had positive MAC blood cultures culture-proven involvement the paranasal sinuses, hard palate, skin, left knee joint. Radiographic studies also...
Objective: To investigate the effect of brain derived neurotrophic factor (BDNF) on mesenchymal stem cells (MSC) inhibiting follicular helper T (Tfh cells). Methods: The contents indoleamine 2,3-dioxygenase (IDO), IL-10, TGF-β and IL-21 in MSC culture supernatant were detected by ELISA; peripheral blood healthy volunteers collected, lymphocyte was separated human separation solution; Co-cultures performed Transwell chamber, proportion CD4(+)CXCR5(+) Tfh their subtypes flow cytometry....
Abstract Background Mycobacterium genavense is an opportunistic pathogen in HIV patients that difficult to culture and manage clinically. Here we describe three cases of with courses representing the spectrum M.genavense presentations current ART era complicated by differing divergent immune responses. Methods Two were a longitudinal study at NIAID enrolling suspected IRIS (PANDORA) (NCT02147405) one was seen St. James’s hospital Dublin. Frozen peripheral blood mononuclear cells collected...
Abstract Tuberculosis associated immune reconstitution inflammatory syndrome (TB-IRIS) is a serious complication of starting combination antiretroviral therapy (cART). TB-IRIS emerges early after cART initiation and characterized by rapid expansions TB-specific CD4+ T cells high levels mediators driven cells. The effects on HIV populations are unknown, but could result in profound expansion elimination infected via cellular activation acute inflammation. We investigated immediate long-term...