- HIV Research and Treatment
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- HIV/AIDS Research and Interventions
- Immunotherapy and Immune Responses
- HIV/AIDS drug development and treatment
- Cytomegalovirus and herpesvirus research
- COVID-19 Clinical Research Studies
- Acute Kidney Injury Research
- Sepsis Diagnosis and Treatment
- SARS-CoV-2 and COVID-19 Research
- HIV-related health complications and treatments
- Systemic Lupus Erythematosus Research
- Animal Disease Management and Epidemiology
- COVID-19 and healthcare impacts
- Long-Term Effects of COVID-19
- Influenza Virus Research Studies
- Thermal Regulation in Medicine
- Lymphoma Diagnosis and Treatment
- Hepatitis C virus research
- Viral Infections and Immunology Research
- Viral-associated cancers and disorders
- Immune responses and vaccinations
- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
Emory University
2021-2025
Instituto Nacional de Enfermedades Respiratorias
2014-2025
Emory National Primate Research Center
2013
LN inflammation in chronic HIV is associated with accumulation of follicular CD8 T cells that could be redirected to kill infected cells.
Current paradigms of CD8 + T cell–mediated protection in HIV infection center almost exclusively on studies peripheral blood, which is thought to provide a window into immune activity at the predominant sites viral replication lymphoid tissues (LTs). Through extensive comparison thoracic duct lymph (TDL), and LTs different species, we show that many LT memory cells bear phenotypic, transcriptional, epigenetic signatures resident (T RMs ). Unlike their circulating counterparts blood or TDL,...
Elite control of HIV replication is linked to polyfunctional lymphoid CD8 + T cells that lack overt cytolytic activity and home B cell follicles.
The persistence of HIV reservoirs, including latently infected, resting CD4+ T cells, is the major obstacle to cure infection. CD32a expression was recently reported mark cells harboring a replication-competent reservoir during antiretroviral therapy (ART) suppression. We aimed determine whether CD32 marks or transcriptionally active infected cells. Using peripheral blood and lymphoid tissue ART-treated HIV+ SIV+ subjects, we found that most circulating memory CD32+ expressed markers...
Elimination of lymphoid tissue reservoirs is a key component HIV eradication strategies. CD8+ T cells play critical role in control HIV, but their functional attributes lymph nodes (LNs) remain unclear. Here, we show that memory, follicular CXCR5+, and HIV-specific from LNs do not manifest the properties cytolytic cells. While frequency CXCR5+ was strongly inversely associated with peripheral viremia, this association dependent on Moreover, poor activity LN linked to compartmentalized...
Abstract The Intact Proviral DNA Assay (IPDA) was developed to address the critical need for a scalable method intact HIV-1 reservoir quantification. This droplet digital PCR-based assay simultaneously targets two regions distinguish genomically proviruses against large background of defective ones, and its application has yielded insights into persistence. Reports failures however, attributed polymorphism, have recently emerged. Here, we describe diverse North American cohort people with...
Abstract Understanding the complexity of long-lived HIV reservoir during antiretroviral therapy (ART) remains a considerable impediment in research towards cure for HIV. To address this, we developed single-cell strategy to precisely define unperturbed peripheral blood HIV-infected memory CD4 + T cell from ART-treated people living with (ART-PLWH) via presence integrated accessible proviral DNA concert epigenetic and surface protein profiling. We identified profound heterogeneity within...
Systemic lupus erythematosus (SLE) is characterized by dysregulated humoral immunity, leading to the generation of autoreactive B cells that can differentiate both within and outside lymph node (LN) follicles. Here, we employed spatial transcriptomics multiplex imaging investigate follicular immune landscaping in situ transcriptomic profile LNs from SLE individuals. Our analysis revealed robust type I IFN plasma cell signatures compared reactive, control Cell deconvolution T subsets are...
HIV-1 persists as a latent infection in CD4 + T cells that can be found lymphoid tissues infected individuals during ART. However, the importance of this tissue reservoir and its contribution to viral rebound upon ART interruption are not clear. In study, we sought compare from blood lymph node five HIV-1-infected individuals. Further, analyzed viruses rebound. We observed frequencies intact proviruses were same node. Moreover, expanded clones bearing identical These sequences did appear...
A high proportion of critically ill patients with COVID-19 develop acute kidney injury (AKI) and die. The early recognition subclinical AKI could contribute to prevention. Therefore, this study was aimed at exploring the role urinary biomarkers NGAL [TIMP-2] × [IGFBP7] for detection in population. This prospective, longitudinal cohort included without entry. Urine samples were collected on admission critical care areas determination concentrations. demographic information, comorbidities,...
Human immunodeficiency virus (HIV) persistence during antiretroviral therapy (ART) is associated with heightened plasma interleukin-10 (IL-10) levels and PD-1 expression. We hypothesized that IL-10 blockade would lead to control of viral rebound following analytical treatment interruption (ATI). Twenty-eight ART-treated, simian (SIV)mac
Follicular helper CD4+ T cells (TFH) play an integral role in promoting B cell differentiation and affinity maturation. Whereas TFH frequencies are increased lymph nodes (LNs) from individuals infected with HIV, humoral immunity remains impaired during chronic HIV infection. Whether inhibits responses LNs unclear. Advances this area have been limited by the difficulty of accessing human lymphoid tissues. Here, we combined high-dimensional mass cytometry receptor repertoire sequencing to...
<title>Abstract</title> Immunotherapeutic approaches to eliminate latently HIV-infected cells are focused on the adaptive immune system. Herein we provide mechanistic evidence for a molecular cascade characterized by epigenetic reprogramming of innate myeloid and CD4 T cells. The coordinate regulation gene expression mediated transcription factors (TFs) IRF3, IRF7, STAT1 C/EBPβ versus AP-1, promoted development antiviral immunity in these which was associated with control viral load decay...
In contrast to pathogenic HIV/SIV infections of humans and rhesus macaques (RMs), natural SIV infection sooty mangabeys (SMs) is typically non-pathogenic despite high viremia. Several studies suggested that low immune activation relative resistance CD4+ central memory T-cells from virus are mechanisms protect SMs AIDS. 2008 it was reported plasmacytoid dendritic cells (pDCs) exhibit attenuated interferon-alpha (IFN-α) responses TLR7/9 ligands in vitro, species-specific amino acid...
CD4+ T cells subsets have a wide range of important helper and regulatory functions in the immune system. Several studies specifically suggested that circulating effector may play direct role control HIV replication through cytolytic activity or autocrine β-chemokine production. However, it remains unclear whether expressing molecules β-chemokines are present within lymph nodes (LNs), major site replication. Here, we report expression enriched cell population with high levels T-box...
CXCR5 is a key marker of follicular helper T (TFH) cells. Using primary lymph nodes (LNs) from HIV-infected patients, we identified population CXCR5− CD4+ cells with TFH-cell-like features. This subset becomes expanded in severe HIV infection and characterized by the upregulation activation markers high PD-1 ICOS surface expression. Integrated analyses on phenotypic heterogeneity, functional capacity, cell receptor (TCR) repertoire, transcriptional profile, epigenetic state CXCR5−PD-1+ICOS+...
CD4 T cells are key mediators of adaptive immune responses during infection and vaccination. Within secondary lymphoid organs, helper cells, particularly those residing in germinal centers known as follicular (Tfh), provide critical help to B-cells promote their survival, isotype switching selection high affinity memory B-cells. On the other hand, important role Tfh for maintenance HIV reservoir is well documented. Thus, interrogating better understanding tissue specific micro-environment...
Global population immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is accumulating through heterogeneous combinations of infection and vaccination. Vaccine distribution in low- middle-income countries has been variable reliant on diverse vaccine platforms. We studied B-cell Mexico, a country where five different vaccines have deployed populations with high SARS-CoV-2 incidences. Levels antibodies that bound stabilized prefusion spike trimer, neutralizing antibody...
CD4
The integration of HIV DNA into the host genome contributes to lifelong infection in most individuals. Few studies have examined lymphoid tissue, where predominantly persists before and after antiretroviral treatment (ART). Of particular interest is whether site distributions differ between stages with paired blood tissue comparisons. Here, we profiled sorted memory, tissue-resident, and/or follicular helper CD4+ T cell subsets from samples acute, chronic, ART-treated We observed minor...
Follicular helper CD4hi T cells (TFH) are a major cellular pool for the maintenance of HIV reservoir. Therefore, delineation follicular (F)/germinal center (GC) immune landscape will significantly advance our understanding pathogenesis. We have applied multiplex confocal imaging, in combination with relevant computational tools, to investigate F/GC situ dynamics viremic (vir-HIV), antiretroviral-treated (cART HIV) People Living With (PLWH) and compare them reactive, non-infected controls....