Scholars@Duke
Roger Keith Reeves

Roger Keith Reeves

Professor in Surgery
Surgery, Surgical Sciences

Selected Publications

Knockdowns of CD3zeta Chain in Primary NK Cells Illustrate Modulation of Antibody-Dependent Cellular Cytotoxicity Against Human Immunodeficiency Virus-1.

Journal Article AIDS Res Hum Retroviruses · November 2024 Multifaceted natural killer (NK) cell activities are indispensable for controlling human immunodeficiency virus (HIV)-1 transmission and pathogenesis. Among the diverse functions of NK cells, antibody-dependent cellular cytotoxicity (ADCC) has been shown t ... Full text Link to item Cite

The Climate Change Burden on Immune Health: Are Persons Living with HIV More at Risk?

Journal Article AIDS Res Hum Retroviruses · October 2024 Climate change poses one of the most significant modern threats to overall human health,especially for vulnerable populations including persons living with HIV (PLWH). In this perspective, we specifically explore the concept of immune resilience in human h ... Full text Link to item Cite

FcαRI (CD89) is upregulated on subsets of mucosal and circulating NK cells and regulates IgA-class specific signaling and functions.

Journal Article Mucosal Immunol · August 2024 Immunoglobulin A (IgA) is the predominant mucosal antibody class with both anti- and pro-inflammatory roles1-3. However, the specific role of the IgA receptor cluster of differentiation (CD)89, expressed by a subset of natural killer (NK) cells, is poorly ... Full text Link to item Cite

NK cells modulate in vivo control of SARS-CoV-2 replication and suppression of lung damage.

Journal Article PLoS Pathog · August 2024 Natural killer (NK) cells play a critical role in virus control. However, it has remained largely unclear whether NK cell mobilization in SARS-CoV-2 infections is beneficial or pathologic. To address this deficit, we employed a validated experimental NK ce ... Full text Link to item Cite

Natural killer-like B cells are a distinct but infrequent innate immune cell subset modulated by SIV infection of rhesus macaques.

Journal Article PLoS Pathog · May 2024 Natural killer-like B (NKB) cells are unique innate immune cells expressing both natural killer (NK) and B cell receptors. As first responders to infection, they secrete IL-18 to induce a critical cascade of innate and adaptive immune cell infiltration and ... Full text Link to item Cite

Antigen-specific memory NK cell responses against HIV and influenza use the NKG2/HLA-E axis.

Journal Article Sci Immunol · December 8, 2023 Multiple studies have broadened the roles of natural killer (NK) cells functioning as purely innate lymphocytes by demonstrating that they are capable of putative antigen-specific immunological memory against multiple infectious agents including HIV-1 and ... Full text Link to item Cite

SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells.

Journal Article Nat Immunol · December 2023 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA generally becomes undetectable in upper airways after a few days or weeks postinfection. Here we used a model of viral infection in macaques to address whether SARS-CoV-2 persists in the body ... Full text Link to item Cite

Multiplex interrogation of the NK cell signalome reveals global downregulation of CD16 signaling during lentivirus infection through an IL-18/ADAM17-dependent mechanism.

Journal Article PLoS Pathog · September 2023 Despite their importance, natural killer (NK) cell responses are frequently dysfunctional during human immunodeficiency virus-1 (HIV-1) and simian immunodeficiency virus (SIV) infections, even irrespective of antiretroviral therapies, with poorly understoo ... Full text Link to item Cite

Multiplex Analysis of Cytokines and Chemokines in Persons Aging With or Without HIV.

Journal Article AIDS Res Hum Retroviruses · July 2023 People with HIV (PWH) on combination antiretroviral therapy (cART) are living longer lives due to modern cART advances and increased routine medical care. The full landscape of aging with HIV is unclear; given that HIV emerged relatively recently in human ... Full text Link to item Cite

Protocol for identification and computational analysis of human natural killer cells using flow cytometry and R.

Journal Article STAR Protoc · March 17, 2023 Identifying differential protein expression is routinely used to delineate natural killer (NK) cells from various sample cohorts. This protocol describes key steps for NK cell analysis: identifying human NK cells using flow gating, data export from FlowJo, ... Full text Link to item Cite

Natural Killer Cells Regulate Acute SIV Replication, Dissemination, and Inflammation, but Do Not Impact Independent Transmission Events.

Journal Article J Virol · January 31, 2023 Natural killer (NK) cells are potent effector cells of the innate immune system possessing both cytotoxic and immunoregulatory capabilities, which contribute to their crucial role in controlling human immunodeficiency virus (HIV) and simian immunodeficienc ... Full text Link to item Cite

Multivariate analysis of FcR-mediated NK cell functions identifies unique clustering among humans and rhesus macaques

Conference Frontiers in Immunology · January 1, 2023 Rhesus macaques (RMs) are a common pre-clinical model used to test HIV vaccine efficacy and passive immunization strategies. Yet, it remains unclear to what extent the Fc-Fc receptor (FcR) interactions impacting antiviral activities of antibodies in RMs re ... Full text Cite

NK cell education: Physiological and pathological influences.

Journal Article Front Immunol · 2023 Natural killer (NK) cells represent a critical defense against viral infections and cancers. NK cells require integration of activating and inhibitory NK cell receptors to detect target cells and the balance of these NK cell inputs defines the global NK ce ... Full text Open Access Link to item Cite

Perturbation of mucosal granulocytic effector cells in lentivirus infections

Conference JOURNAL OF THE INTERNATIONAL AIDS SOCIETY · 2023 Cite

Multivariate analysis of FcR-mediated NK cell functions identifies unique clustering among humans and rhesus macaques.

Journal Article Front Immunol · 2023 Rhesus macaques (RMs) are a common pre-clinical model used to test HIV vaccine efficacy and passive immunization strategies. Yet, it remains unclear to what extent the Fc-Fc receptor (FcR) interactions impacting antiviral activities of antibodies in RMs re ... Full text Open Access Link to item Cite

A genetically engineered, stem-cell-derived cellular vaccine.

Journal Article Cell Rep Med · December 20, 2022 Despite rapid clinical translation of COVID-19 vaccines in response to the global pandemic, an opportunity remains for vaccine technology innovation to address current limitations and meet challenges of inevitable future pandemics. We describe a universal ... Full text Open Access Link to item Cite

Mucosal-homing natural killer cells are associated with aging in persons living with HIV.

Journal Article Cell Rep Med · October 18, 2022 Natural killer (NK) cells are critical modulators of HIV transmission and disease. Recent evidence suggests a loss of NK cell cytotoxicity during aging, yet analysis of NK cell biology and aging in people with HIV (PWH) is lacking. Herein, we perform compr ... Full text Link to item Cite

The functional diversity of tissue-resident natural killer cells against infection.

Journal Article Immunology · September 2022 For decades, studies of natural killer (NK) cells have focused on those found in peripheral blood (PBNK cells) as the prototype for NK cell biology. Only recently have researchers begun to explore the diversity of tissue-resident NK (tr-NK) cells. While tr ... Full text Link to item Cite

Call for Papers: AIDS Research and Human Retroviruses.

Journal Article AIDS Res Hum Retroviruses · February 2022 Full text Link to item Cite

Learning to Be Elite: Lessons From HIV-1 Controllers and Animal Models on Trained Innate Immunity and Virus Suppression.

Journal Article Front Immunol · 2022 Although antiretroviral therapy (ART) has drastically changed the lives of people living with human immunodeficiency virus-1 (HIV-1), long-term treatment has been associated with a vast array of comorbidities. Therefore, a cure for HIV-1 remains the best o ... Full text Link to item Cite

Altered Innate Immunity and Damaged Epithelial Integrity in Vaginal Microbial Dysbiosis.

Journal Article Front Reprod Health · 2022 The role of neutrophils relative to vaginal dysbiosis is unclear. We hypothesize that bacterial vaginosis (BV)-associated bacteria may induce the activation and accumulation of mucosal neutrophils within the female reproductive tract (FRT), resulting in ep ... Full text Link to item Cite

Call for Papers: AIDS Research and Human Retroviruses.

Journal Article AIDS Res Hum Retroviruses · January 2022 Full text Link to item Cite

Increased IL-6 expression precedes reliable viral detection in the rhesus macaque brain during acute SIV infection.

Journal Article JCI Insight · October 22, 2021 Knowledge of immune activation in the brain during acute HIV infection is crucial for the prevention and treatment of HIV-associated neurological disorders. We determined regional brain (basal ganglia, thalamus, and frontal cortex) immune and virological p ... Full text Link to item Cite

Systemic and mucosal mobilization of granulocyte subsets during lentiviral infection.

Journal Article Immunology · October 2021 Granulocytes mediate broad immunoprotection through phagocytosis, extracellular traps, release of cytotoxic granules, antibody effector functions and recruitment of other immune cells against pathogens. However, descriptions of granulocytes in HIV infectio ... Full text Link to item Cite

Identification of the predominant human NK cell effector subset mediating ADCC against HIV-infected targets coated with BNAbs or plasma from PLWH.

Journal Article Eur J Immunol · August 2021 The potential of immunotherapy strategies utilizing broadly neutralizing antibodies (BNAbs), such as 3BNC117 and 10-1074, to limit viral replication while also facilitating clearance of HIV infected cells has heightened interest in identifying the predomin ... Full text Link to item Cite

Probiotic supplementation reduces inflammatory profiles but does not prevent oral immune perturbations during SIV infection.

Journal Article Sci Rep · July 15, 2021 HIV/SIV infections lead to massive loss of mucosal CD4 + T cells and breakdown of the epithelial mucosa resulting in severe microbial dysbiosis and chronic immune activation that ultimately drive disease progression. Moreover, disruption of one of the most ... Full text Link to item Cite

SIV-induced terminally differentiated adaptive NK cells in lymph nodes associated with enhanced MHC-E restricted activity.

Journal Article Nat Commun · February 24, 2021 Natural killer (NK) cells play a critical understudied role during HIV infection in tissues. In a natural host of SIV, the African green monkey (AGM), NK cells mediate a strong control of SIVagm infection in secondary lymphoid tissues. We demonstrate that ... Full text Open Access Link to item Cite

TRIGGERED: could refocused cell signaling be key to natural killer cell-based HIV immunotherapeutics?

Journal Article AIDS · February 2, 2021 Natural killer (NK) cells are one of the critical innate immune effector cells that directly kill tumors and virus-infected cells, and modulate other immune cells including dendritic cells, CD4+ and CD8+ T cells. Signals from activating and inhibitory surf ... Full text Link to item Cite

Systemic and mucosal mobilization of granulocyte subsets during lentivirus infection

Journal Article · 2021 Granulocytes mediate broad immunoprotection through phagocytosis, extracellular traps, release of cytotoxic granules, antibody effector functions and recruitment of other immune cells against pathogens. However, descriptions of granulocytes in HIV infectio ... Full text Cite

Skipped Over: Tuning Natural Killer Cells Toward HIV Through Alternative Splicing.

Journal Article AIDS Res Hum Retroviruses · December 2020 Natural killer (NK) cells provide some of the earliest immune responses to infection, but when viruses manipulate or perturb the immune environment to alter NK cell function, this places the host at a disadvantage. Indeed, others and we observe that in the ... Full text Link to item Cite

Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques.

Journal Article Nature · October 2020 A safe and effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be required to end the coronavirus disease 2019 (COVID-19) pandemic1-8. For global deployment and pandemic control, a vaccine that requires only a single immu ... Full text Open Access Link to item Cite

Friends or foes? The knowns and unknowns of natural killer cell biology in COVID-19 and other coronaviruses in July 2020.

Journal Article PLoS Pathog · August 2020 The COVID-19 pandemic has caused more than 575,000 deaths worldwide as of mid-July 2020 and still continues globally unabated. Immune dysfunction and cytokine storm complicate the disease, which in turn leads to the question of whether stimulation or suppr ... Full text Link to item Cite

Functional Perturbation of Mucosal Group 3 Innate Lymphoid and Natural Killer Cells in Simian-Human Immunodeficiency Virus/Simian Immunodeficiency Virus-Infected Infant Rhesus Macaques.

Journal Article J Virol · February 14, 2020 Mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) via breastfeeding is responsible for nearly half of new infections of children with HIV. Although innate lymphoid cells (ILC) and natural killer (NK) cells are found throughout the ... Full text Link to item Cite

Characterization of Rhesus Macaque Liver-Resident CD49a+ NK Cells During Retrovirus Infections.

Journal Article Front Immunol · 2020 CD49a+ tissue resident NK cells have been implicated in memory-like NK cell responses, but while this population is well-characterized in mice and in humans, they are poorly described in non-human primates (NHP) which are particularly critical for modeling ... Full text Link to item Cite

Probiotic Supplementation Reduces Inflammatory Profiles But Does Not Prevent Oral Immune Perturbations During SIV Infection

Journal Article · 2020 ABSTRACT HIV/SIV infections lead to massive loss of mucosal CD4+ T cells and breakdown of the epithelial mucosa resulting in severe microbial dysbiosis and chronic immune activation that ultimately drive disease progression. Moreover, disruption o ... Full text Cite

Delineation and Modulation of the Natural Killer Cell Transcriptome in Rhesus Macaques During ZIKV and SIV Infections.

Journal Article Front Cell Infect Microbiol · 2020 Natural killer (NK) cells are crucial regulators of antiviral and anti-tumor immune responses. Although in humans some NK cell transcriptional programs are relatively well-established, NK cell transcriptional networks in non-human primates (NHP) remain poo ... Full text Open Access Link to item Cite

Simian Immunodeficiency Virus Infection Modulates CD94+ (KLRD1+) NK Cells in Rhesus Macaques.

Journal Article J Virol · August 15, 2019 Recently, we and others have shown that natural killer (NK) cells exhibit memory-like recall responses against cytomegalovirus (CMV) and human immunodeficiency/virus simian immunodeficiency virus (HIV/SIV) infections. Although the mechanism(s) have not bee ... Full text Link to item Cite

Semaphorin 7A modulates cytokine-induced memory-like responses by human natural killer cells.

Journal Article Eur J Immunol · August 2019 Cytokine-induced memory-like (CIML) NK cells are endowed with the capacity to mediate enhanced effector functions upon cytokine or activating receptor restimulation for several weeks following short-term preactivation with IL-12, IL-15, and IL-18. Promisin ... Full text Link to item Cite

Adaptive NK cell responses in HIV/SIV infections: A roadmap to cell-based therapeutics?

Journal Article J Leukoc Biol · June 2019 NK cells play a critical role in antiviral and antitumor responses. Although current NK cell immune therapies have focused primarily on cancer biology, many of these advances can be readily applied to target HIV/simian immunodeficiency virus (SIV)-infected ... Full text Link to item Cite

Non-linear multidimensional flow cytometry analyses delineate NK cell phenotypes in normal and HIV-infected chimpanzees.

Journal Article Int Immunol · March 5, 2019 Natural killer (NK) cells are primary immune effector cells with both innate and potentially adaptive functions against viral infections, but commonly become exhausted or dysfunctional during chronic diseases such as human immunodeficiency virus (HIV). Chi ... Full text Link to item Cite

Knowns and Unknowns of Assaying Antibody-Dependent Cell-Mediated Cytotoxicity Against HIV-1.

Journal Article Front Immunol · 2019 It is now well-accepted that Fc-mediated effector functions, including antibody-dependent cellular cytotoxicity (ADCC), can contribute to vaccine-elicited protection as well as post-infection control of HIV viremia. This picture was derived using a wide ar ... Full text Link to item Cite

Monkeying Around: Using Non-human Primate Models to Study NK Cell Biology in HIV Infections.

Journal Article Front Immunol · 2019 Natural killer (NK) cells are the major innate effectors primed to eliminate virus-infected and tumor or neoplastic cells. Recent studies also suggest nuances in phenotypic and functional characteristics among NK cell subsets may further permit execution o ... Full text Link to item Cite

Harvard HIV and Aging Workshop: Perspectives and Priorities from Claude D. Pepper Centers and Centers for AIDS Research.

Journal Article AIDS Res Hum Retroviruses · 2019 People aging with HIV (PAWH) infection experience greater impairments in physical and cognitive function, in addition to higher rates of peripheral comorbid conditions (e.g., renal failure, diabetes, bone fracture, hypertension, cardiovascular disease, pol ... Full text Link to item Cite

Impact of CMV Infection on Natural Killer Cell Clonal Repertoire in CMV-Naïve Rhesus Macaques.

Journal Article Front Immunol · 2019 Recent functional, gene expression, and epigenetic studies have suggested the presence of a subset of mature natural killer (NK) cells responsible for maintaining NK cell memory. The lack of endogenous clonal markers in NK cells impedes understanding the g ... Full text Link to item Cite

A Natural Impact: NK Cells at the Intersection of Cancer and HIV Disease.

Journal Article Front Immunol · 2019 Despite efficient suppression of plasma viremia in people living with HIV (PLWH) on cART, evidence of HIV-induced immunosuppression remains, and normally benign and opportunistic pathogens become major sources of co-morbidities, including virus-induced can ... Full text Open Access Link to item Cite

CMV Primes Functional Alternative Signaling in Adaptive Δg NK Cells but Is Subverted by Lentivirus Infection in Rhesus Macaques.

Journal Article Cell Rep · December 4, 2018 Despite burgeoning evidence demonstrating the adaptive properties of natural killer (NK) cells, mechanistic data explaining these phenomena are lacking. Following antibody sensitization, NK cells lacking the Fc receptor (FcR) signaling chain (Δg) acquire a ... Full text Link to item Cite

Indirect activation of rhesus macaque (Macaca mulatta) NK cells in oral and mucosal draining lymph nodes.

Journal Article J Med Primatol · October 2018 The oral mucosae and draining lymph nodes are primary entry points for invading pathogens, particularly during immunosuppressive HIV/SIV infections. Innate immunity against oral stimuli, including natural killer (NK) cells, is understudied. Herein, we demo ... Full text Link to item Cite

Hallmarks of primate lentiviral immunodeficiency infection recapitulate loss of innate lymphoid cells.

Journal Article Nat Commun · September 27, 2018 Innate lymphoid cells (ILCs) play critical roles in mucosal barrier defense and tissue homeostasis. While ILCs are depleted in HIV-1 infection, this phenomenon is not a generalized feature of all viral infections. Here we show in untreated SIV-infected rhe ... Full text Link to item Cite

Intestinal damage precedes mucosal immune dysfunction in SIV infection.

Journal Article Mucosal Immunol · September 2018 HIV and pathogenic SIV infection are characterized by mucosal dysfunction including epithelial barrier damage, loss of Th17 cells, neutrophil infiltration, and microbial translocation with accompanying inflammation. However, it is unclear how and when thes ... Full text Link to item Cite

Progressive lentivirus infection induces natural killer cell receptor-expressing B cells in the gastrointestinal tract.

Journal Article AIDS · July 31, 2018 OBJECTIVE: Recently, a seemingly novel innate immune cell subset bearing features of natural killer and B cells was identified in mice. So-called NKB cells appear as first responders to infections, but whether this cell population is truly novel or is in f ... Full text Link to item Cite

Adenovirus Vector Vaccination Impacts NK Cell Rheostat Function following Lymphocytic Choriomeningitis Virus Infection.

Journal Article J Virol · June 1, 2018 Natural killer (NK) cells respond rapidly as a first line of defense against infectious pathogens. In addition, NK cells may provide a "rheostat" function and have been shown to reduce the magnitude of antigen-specific T cell responses following infection ... Full text Link to item Cite

Exosome markers associated with immune activation and oxidative stress in HIV patients on antiretroviral therapy.

Journal Article Sci Rep · May 8, 2018 Exosomes are nanovesicles released from most cell types including immune cells. Prior studies suggest exosomes play a role in HIV pathogenesis, but little is known about exosome cargo in relation to immune responses and oxidative stress. Here, we character ... Full text Link to item Cite

Tracking KLRC2 (NKG2C)+ memory-like NK cells in SIV+ and rhCMV+ rhesus macaques.

Journal Article PLoS Pathog · May 2018 Natural killer (NK) cells classically typify the nonspecific effector arm of the innate immune system, but have recently been shown to possess memory-like properties against multiple viral infections, most notably CMV. Expression of the activating receptor ... Full text Link to item Cite

Short Communication: Apoptotic Membrane Microparticles Quantified by Fluorescent Bead-Based Assay Are Elevated in HIV and SIV Infections.

Journal Article AIDS Res Hum Retroviruses · May 2018 Apoptotic membrane microparticles (MMPs) derived from dying cells of multiple cell origins are highly immunostimulatory and are indicative of global immune activation and cell death in a variety of diseases. In this study, we developed a flow cytometric be ... Full text Link to item Cite

Cytokine-Mediated Tissue Injury in Non-human Primate Models of Viral Infections.

Journal Article Front Immunol · 2018 Viral infections trigger robust secretion of interferons and other antiviral cytokines by infected and bystander cells, which in turn can tune the immune response and may lead to viral clearance or immune suppression. However, aberrant or unrestricted cyto ... Full text Link to item Cite

Lymph Node Cellular and Viral Dynamics in Natural Hosts and Impact for HIV Cure Strategies.

Journal Article Front Immunol · 2018 Combined antiretroviral therapies (cARTs) efficiently control HIV replication leading to undetectable viremia and drastic increases in lifespan of people living with HIV. However, cART does not cure HIV infection as virus persists in cellular and anatomica ... Full text Link to item Cite

Hepatic immunopathology during occult hepacivirus re-infection.

Journal Article Virology · December 2017 Despite drug advances for Hepatitis C virus (HCV), re-infections remain prevalent in high-risk populations. Unfortunately, the role of preexisting viral immunity and how it modulates re-infection is unclear. GBV-B infection of common marmosets is a useful ... Full text Link to item Cite

Natural killer cells migrate into and control simian immunodeficiency virus replication in lymph node follicles in African green monkeys.

Journal Article Nat Med · November 2017 Natural killer (NK) cells play an essential role in antiviral immunity, but knowledge of their function in secondary lymphoid organs is incomplete. Lymph node follicles constitute a major viral reservoir during infections with HIV-1 and simian immunodefici ... Full text Link to item Cite

Innate Lymphoid Cells in HIV/SIV Infections.

Journal Article Front Immunol · 2017 Over the past several years, new populations of innate lymphocytes have been described in mice and primates that are critical for mucosal homeostasis, microbial regulation, and immune defense. Generally conserved from mice to humans, innate lymphoid cells ... Full text Link to item Cite

Metabolic Dysregulation in Hepacivirus Infection of Common Marmosets (Callithrix jacchus).

Journal Article PLoS One · 2017 Chronic hepatitis C has been associated with metabolic syndrome that includes insulin resistance, hepatic steatosis and obesity. These metabolic aberrations are risk factors for disease severity and treatment outcome in infected patients. Experimental infe ... Full text Link to item Cite

Persistent Low-Level Replication of SIVΔnef Drives Maturation of Antibody and CD8 T Cell Responses to Induce Protective Immunity against Vaginal SIV Infection.

Journal Article PLoS Pathog · December 2016 Defining the correlates of immune protection conferred by SIVΔnef, the most effective vaccine against SIV challenge, could enable the design of a protective vaccine against HIV infection. Here we provide a comprehensive assessment of immune responses that ... Full text Link to item Cite

Acute Liver Damage Associated with Innate Immune Activation in a Small Nonhuman Primate Model of Hepacivirus Infection.

Journal Article J Virol · October 15, 2016 UNLABELLED: Despite its importance in shaping adaptive immune responses, viral clearance, and immune-based inflammation, tissue-specific innate immunity remains poorly characterized for hepatitis C virus (HCV) infection due to the lack of access to acutely ... Full text Link to item Cite

Enhancement of Microbiota in Healthy Macaques Results in Beneficial Modulation of Mucosal and Systemic Immune Function.

Journal Article J Immunol · March 1, 2016 Given the critical role of mucosal surfaces in susceptibility to infection, it is imperative that effective mucosal responses are induced when developing efficacious vaccines and prevention strategies for infection. Modulating the microbiota in the gastroi ... Full text Link to item Cite

SIV-induced Translocation of Bacterial Products in the Liver Mobilizes Myeloid Dendritic and Natural Killer Cells Associated With Liver Damage.

Journal Article J Infect Dis · February 1, 2016 Disruption of the mucosal epithelium during lentivirus infections permits translocation of microbial products into circulation, causing immune activation and driving disease. Although the liver directly filters blood from the intestine and is the first lin ... Full text Link to item Cite

Targeting the gastrointestinal tract to develop novel therapies for HIV.

Journal Article Clin Pharmacol Ther · October 2015 Despite the use of antiretroviral therapy (ART), which delays and/or prevents AIDS pathogenesis, human immunodeficiency virus (HIV)-infected individuals continue to face increased morbidities and mortality rates compared with uninfected individuals. Gastro ... Full text Link to item Cite

NK cell exhaustion: bad news for chronic disease?

Journal Article Oncotarget · September 8, 2015 Full text Link to item Cite

Antigen-specific NK cell memory in rhesus macaques.

Journal Article Nat Immunol · September 2015 Natural killer (NK) cells have traditionally been considered nonspecific components of innate immunity, but recent studies have shown features of antigen-specific memory in mouse NK cells. However, it has remained unclear whether this phenomenon also exist ... Full text Link to item Cite

Accumulation of Cytotoxic CD16+ NK Cells in Simian Immunodeficiency Virus-Infected Lymph Nodes Associated with In Situ Differentiation and Functional Anergy.

Journal Article J Virol · July 2015 UNLABELLED: Recent evidence suggests that even in treated infections, human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication may continue in lymph nodes (LN), serving as a potential virus reservoir. Here we investigated the ... Full text Link to item Cite

Bone marrow-imprinted gut-homing of plasmacytoid dendritic cells (pDCs) in acute simian immunodeficiency virus infection results in massive accumulation of hyperfunctional CD4+ pDCs in the mucosae.

Journal Article J Infect Dis · June 1, 2015 Plasmacytoid dendritic cells (pDCs), a primary source of interferon α (IFN-α), provide a first line of innate immune defense against human immunodeficiency virus infection. However, their kinetics and functions during acute infection are poorly understood. ... Full text Link to item Cite

Characterization of CD8+ T cell differentiation following SIVΔnef vaccination by transcription factor expression profiling.

Journal Article PLoS Pathog · March 2015 The onset of protective immunity against pathogenic SIV challenge in SIVΔnef-vaccinated macaques is delayed for 15-20 weeks, a process that is related to qualitative changes in CD8+ T cell responses induced by SIVΔnef. As a novel approach to characterize c ... Full text Link to item Cite

CD8 T cell response maturation defined by anentropic specificity and repertoire depth correlates with SIVΔnef-induced protection.

Journal Article PLoS Pathog · February 2015 The live attenuated simian immunodeficiency virus (LASIV) vaccine SIVΔnef is one of the most effective vaccines in inducing protection against wild-type lentiviral challenge, yet little is known about the mechanisms underlying its remarkable protective eff ... Full text Link to item Cite

Hypercytotoxicity and rapid loss of NKp44+ innate lymphoid cells during acute SIV infection.

Journal Article PLoS Pathog · December 2014 HIV/SIV infections break down the integrity of the gastrointestinal mucosa and lead to chronic immune activation and associated disease progression. Innate lymphoid cells (ILCs), distinguishable by high expression of NKp44 and RORγt, play key roles in muco ... Full text Link to item Cite

Short communication: Plasmacytoid dendritic cells from HIV-1 Elite Controllers maintain a gut-homing phenotype associated with immune activation.

Journal Article AIDS Res Hum Retroviruses · December 2014 Lentivirus infections are characterized by a dramatic loss of mucosal CD4(+) T cells, breakdown of the gut mucosa, and subsequent chronic immune activation. Residual immune activation persists even in patients controlling virus replication and remains a si ... Full text Link to item Cite

Transcriptional profiling of peripheral CD8+T cell responses to SIVΔnef and SIVmac251 challenge reveals a link between protective immunity and induction of systemic immunoregulatory mechanisms.

Journal Article Virology · November 2014 Immunization of macaques with attenuated simian immunodeficiency virus (SIV) with deletions in nef (SIVΔnef) is shown to elicit protective immunity to infection by pathogenic SIV, yet the mechanisms that orchestrate protection and prevent pathogenesis rema ... Full text Link to item Cite

Live simian immunodeficiency virus vaccine correlate of protection: local antibody production and concentration on the path of virus entry.

Journal Article J Immunol · September 15, 2014 We sought design principles for a vaccine to prevent HIV transmission to women by identifying correlates of protection conferred by a highly effective live attenuated SIV vaccine in the rhesus macaque animal model. We show that SIVmac239Δnef vaccination re ... Full text Link to item Cite

Innate Immunity in Simian Immunodeficiency Virus Infection

Chapter · July 10, 2014 The past decade has seen the emergence of innate immunity as a mature field. The study of innate immunity has had a significant impact on the concepts of HIV immunity, pathogenesis, and vaccines. In this chapter, basic concepts of innate immunity at the an ... Full text Cite

NK cell responses to simian immunodeficiency virus vaginal exposure in naive and vaccinated rhesus macaques.

Journal Article J Immunol · July 1, 2014 NK cell responses to HIV/SIV infection have been well studied in acute and chronic infected patients/monkeys, but little is known about NK cells during viral transmission, particularly in mucosal tissues. In this article, we report a systematic study of NK ... Full text Link to item Cite

Modeling HCV disease in animals: virology, immunology and pathogenesis of HCV and GBV-B infections.

Journal Article Front Microbiol · 2014 Hepatitis C virus (HCV) infection has become a global public health burden costing billions of dollars in health care annually. Even with rapidly advancing scientific technologies this disease still poses a significant threat due to a lack of vaccines and ... Full text Link to item Cite

All-trans-retinoic acid imprints expression of the gut-homing marker α4β7 while suppressing lymph node homing of dendritic cells.

Journal Article Clin Vaccine Immunol · October 2013 Tissue-directed trafficking of dendritic cells (DCs) as natural adjuvants and/or direct vaccine carriers is highly attractive for the next generation of vaccines and immunotherapeutics. Since these types of studies would undoubtedly be first conducted usin ... Full text Link to item Cite

Loss of bone marrow NK cells during SIV infection is associated with increased turnover rates and cytotoxicity but not changes in trafficking.

Journal Article J Med Primatol · October 2013 BACKGROUND: HIV and SIV infections induce NK cell dysfunction and hematopoietic defects in the bone marrow, but the effects of infection on bone marrow NK cell development and function are unknown. METHODS: Bone marrow NK cells were analyzed from both naïv ... Full text Link to item Cite

Multi-functional plasmacytoid dendritic cells redistribute to gut tissues during simian immunodeficiency virus infection.

Journal Article Immunology · October 2013 The objective of this study was to determine the systemic effects of chronic simian immunodeficiency virus (SIV) infection on plasmacytoid dendritic cells (pDCs). pDCs play a critical role in antiviral immunity, but current data are conflicting on whether ... Full text Link to item Cite

Characterization of circulating natural killer cells in neotropical primates.

Journal Article PLoS One · 2013 Despite extensive use of nonhuman primates as models for infectious diseases and reproductive biology, imprecise phenotypic and functional definitions exist for natural killer (NK) cells. This deficit is particularly significant in the burgeoning use of sm ... Full text Link to item Cite

Location and dynamics of the immunodominant CD8 T cell response to SIVΔnef immunization and SIVmac251 vaginal challenge.

Journal Article PLoS One · 2013 Live-attenuated SIV vaccines (LAVs) have been the most effective to date in preventing or partially controlling infection by wild-type SIV in non-human primate models of HIV-1 transmission to women acting by mechanisms of protection that are not well under ... Full text Link to item Cite

Monkeypox virus infection of rhesus macaques induces massive expansion of natural killer cells but suppresses natural killer cell functions.

Journal Article PLoS One · 2013 Natural killer (NK) cells play critical roles in innate immunity and in bridging innate and adaptive immune responses against viral infection. However, the response of NK cells to monkeypox virus (MPXV) infection is not well characterized. In this intraven ... Full text Link to item Cite

No monkey business: why studying NK cells in non-human primates pays off.

Journal Article Front Immunol · 2013 Human NK (hNK) cells play a key role in mediating host immune responses against various infectious diseases. For practical reasons, the majority of the data on hNK cells has been generated using peripheral blood lymphocytes. In contrast, our knowledge of N ... Full text Link to item Cite

SIV infection induces accumulation of plasmacytoid dendritic cells in the gut mucosa.

Journal Article J Infect Dis · November 2012 Multiple studies suggest that plasmacytoid dendritic cells (pDCs) are depleted and dysfunctional during human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) infection, but little is known about pDCs in the gut-the primary site of virus repl ... Full text Link to item Cite

Functional perturbation of classical natural killer and innate lymphoid cells in the oral mucosa during SIV infection.

Journal Article Front Immunol · 2012 Despite the fact that the majority of human pathogens are transmitted across mucosal surfaces, including the oral mucosae, oral immunity is poorly understood. Furthermore, because the normal flora of the oral cavity is vast and significantly diverse, host ... Full text Link to item Cite

ADCC develops over time during persistent infection with live-attenuated SIV and is associated with complete protection against SIV(mac)251 challenge.

Journal Article PLoS Pathog · 2012 Live-attenuated strains of simian immunodeficiency virus (SIV) routinely confer apparent sterilizing immunity against pathogenic SIV challenge in rhesus macaques. Understanding the mechanisms of protection by live-attenuated SIV may provide important insig ... Full text Link to item Cite

Gut inflammation and indoleamine deoxygenase inhibit IL-17 production and promote cytotoxic potential in NKp44+ mucosal NK cells during SIV infection.

Journal Article Blood · September 22, 2011 Natural killer (NK) cells are classically viewed as effector cells that kill virus-infected and neoplastic cells, but recent studies have identified a rare mucosal NK- cell subpopulation secreting the TH17 cytokine IL-22. Here, we report identification of ... Full text Link to item Cite

Flow cytometry based identification of simian immunodeficiency virus Env-specific B lymphocytes.

Journal Article J Immunol Methods · July 29, 2011 SIV infection of macaques is the most widely employed model for preclinical AIDS vaccine and pathogenesis research. In macaques, high-titer virus-specific antibodies are induced by infection, and antibody responses can drive evolution of viral escape varia ... Full text Link to item Cite

Characterization of killer immunoglobulin-like receptor genetics and comprehensive genotyping by pyrosequencing in rhesus macaques.

Journal Article BMC Genomics · June 7, 2011 BACKGROUND: Human killer immunoglobulin-like receptors (KIRs) play a critical role in governing the immune response to neoplastic and infectious disease. Rhesus macaques serve as important animal models for many human diseases in which KIRs are implicated; ... Full text Link to item Cite

Potential confusion of contaminating CD16+ myeloid DCs with anergic CD16+ NK cells in chimpanzees.

Journal Article Eur J Immunol · April 2011 Precise identification of NK-cell populations in humans and nonhuman primates has been confounded by imprecise phenotypic definitions. A common definition used in nonhuman primates, including chimpanzees, is CD3(-) CD8α(+) CD16(+) , and this is the dominan ... Full text Link to item Cite

Quantification of mucosal mononuclear cells in tissues with a fluorescent bead-based polychromatic flow cytometry assay.

Journal Article J Immunol Methods · March 31, 2011 Since the vast majority of infections occur at mucosal surfaces, accurate characterization of mucosal immune cells is critically important for understanding transmission and control of infectious diseases. Standard flow cytometric analysis of cells obtaine ... Full text Link to item Cite

KIR polymorphisms modulate peptide-dependent binding to an MHC class I ligand with a Bw6 motif.

Journal Article PLoS Pathog · March 2011 Molecular interactions between killer immunoglobulin-like receptors (KIRs) and their MHC class I ligands play a central role in the regulation of natural killer (NK) cell responses to viral pathogens and tumors. Here we identify Mamu-A1*00201 (Mamu-A*02), ... Full text Open Access Link to item Cite

Simian immunodeficiency virus infection induces expansion of alpha4beta7+ and cytotoxic CD56+ NK cells.

Journal Article J Virol · September 2010 Herein we demonstrate that chronic simian immunodeficiency virus (SIV) infection induces significant upregulation of the gut-homing marker alpha4beta7 on macaque NK cells, coupled with downregulation of the lymph node-trafficking marker, CCR7. Interestingl ... Full text Link to item Cite

Mobilization of CD34+ progenitor cells in association with decreased proliferation in the bone marrow of macaques after administration of the Fms-like tyrosine kinase 3 ligand.

Journal Article Clin Vaccine Immunol · August 2010 Fms-like tyrosine kinase 3 ligand (FLT3-L) is critical for the differentiation and self-renewal of CD34+ progenitor cells in primates and has been used therapeutically to mobilize progenitor and dendritic cells in vivo. However, little is known regarding t ... Full text Link to item Cite

CD16- natural killer cells: enrichment in mucosal and secondary lymphoid tissues and altered function during chronic SIV infection.

Journal Article Blood · June 3, 2010 Natural killer (NK) cells contribute to control of HIV/SIV infection. We defined macaque NK-cell subsets based on expression of CD56 and CD16 and found their distribution to be highly disparate. CD16(+) NK cells predominated in peripheral blood, whereas mo ... Full text Link to item Cite

Inhibitory TCR coreceptor PD-1 is a sensitive indicator of low-level replication of SIV and HIV-1.

Journal Article J Immunol · January 1, 2010 Ongoing antigenic stimulation appears to be an important prerequisite for the persistent expression of programmed death 1 (PD-1), an inhibitory TCR coreceptor of the CD28 family. Although recent publications have emphasized the utility of PD-1 as a marker ... Full text Link to item Cite

Systemic dendritic cell mobilization associated with administration of FLT3 ligand to SIV- and SHIV-infected macaques.

Journal Article AIDS Res Hum Retroviruses · December 2009 Reports indicate that myeloid and plasmacytoid dendritic cells (mDCs and pDCs), which are key effector cells in host innate immune responses, can be infected with HIV-1 and are reduced in number and function during the chronic phase of HIV disease. Further ... Full text Link to item Cite

Vaccination with SIVmac239Deltanef activates CD4+ T cells in the absence of CD4 T-cell loss.

Journal Article J Med Primatol · October 2009 BACKGROUND: Pathogenic HIV and SIV infections characteristically deplete central memory CD4(+) T cells and induce chronic immune activation, but it is controversial whether this also occurs after vaccination with attenuated SIVs and whether depletion or ac ... Full text Link to item Cite

Characterization of plasmacytoid dendritic cells in bone marrow of pig-tailed macaques.

Journal Article Clin Vaccine Immunol · January 2008 Plasmacytoid dendritic cells (pDCs), one of two types of bone marrow (BM)-derived blood DCs, play an important role in linking innate and adaptive immune responses. However, little is known about the nature of pDCs that reside in the BM. Because the simian ... Full text Link to item Cite

Disparate effects of acute and chronic infection with SIVmac239 or SHIV-89.6P on macaque plasmacytoid dendritic cells.

Journal Article Virology · September 1, 2007 Blood plasmacytoid dendritic cells (pDCs) contribute to both innate and adaptive immune responses by secreting high levels of IFN-alpha following acute bacterial and viral infections and indirectly by augmenting cell-mediated immunity. Cross-sectional stud ... Full text Link to item Cite

Placental immunopathology and pregnancy failure in the FIV-infected cat.

Journal Article Placenta · 2005 Placental HIV infections frequently result in infected babies or miscarriage. Aberrant placental cytokine expression during HIV infections may facilitate transplacental viral transmission or pregnancy perturbation. The feline immunodeficiency virus (FIV)-i ... Full text Link to item Cite