Scholars@Duke
Cordelia Manickam

Cordelia Manickam

Assistant 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Adjuvant effects of invariant NKT cell ligand potentiates the innate and adaptive immunity to an inactivated H1N1 swine influenza virus vaccine in pigs.

Journal Article Vet Microbiol · April 15, 2016 Pigs are considered as the source of some of the emerging human flu viruses. Inactivated swine influenza virus (SwIV) vaccine has been in use in the US swine herds, but it failed to control the flu outbreaks. The main reason has been attributed to lack of ... 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

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

An innovative approach to induce cross-protective immunity against porcine reproductive and respiratory syndrome virus in the lungs of pigs through adjuvanted nanotechnology-based vaccination.

Journal Article Int J Nanomedicine · 2014 Porcine reproductive and respiratory syndrome (PRRS) is an economically devastating respiratory disease of pigs. The disease is caused by the PRRS virus (PRRSV), an Arterivirus which is a highly mutating RNA virus. Widely used modified live PRRSV vaccines ... Full text Link to item Cite

Pretreatment of epithelial cells with live Streptococcus pneumoniae has no detectable effect on influenza A virus replication in vitro.

Journal Article PLoS One · 2014 Influenza A virus (IAV) and Streptococcus pneumoniae (pneumococcus) are two major upper respiratory tract pathogens responsible for exacerbated disease in coinfected individuals. Despite several studies showing increased susceptibility to secondary bacteri ... Full text Link to item Cite

Adjuvanted poly(lactic-co-glycolic) acid nanoparticle-entrapped inactivated porcine reproductive and respiratory syndrome virus vaccine elicits cross-protective immune response in pigs.

Journal Article Int J Nanomedicine · 2014 Porcine reproductive and respiratory syndrome (PRRS), caused by the PRRS virus (PRRSV), is an economically devastating disease, causing daily losses of approximately $3 million to the US pork industry. Current vaccines have failed to completely prevent PRR ... Full text Link to item Cite

PLGA nanoparticle entrapped killed porcine reproductive and respiratory syndrome virus vaccine helps in viral clearance in pigs.

Journal Article Vet Microbiol · September 27, 2013 Porcine reproductive and respiratory syndrome (PRRS) is a chronic viral disease of pigs, has been posing a huge economic concern to pig industry worldwide. In this study, we developed biodegradable PLGA [poly(d,l-lactide-co-glycolide)] nanoparticle-entrapp ... Full text Link to item Cite

Porcine reproductive and respiratory syndrome virus induces pronounced immune modulatory responses at mucosal tissues in the parental vaccine strain VR2332 infected pigs.

Journal Article Vet Microbiol · February 22, 2013 Porcine reproductive and respiratory syndrome (PRRS) is a chronic viral disease of pigs caused by PRRS virus (PRRSV). The PRRSV VR2332 is the prototype North American parental strain commonly used in the preparation of vaccines. Goal of this study was to u ... Full text Link to item Cite

Mycobacterium tuberculosis whole cell lysate enhances proliferation of CD8 positive lymphocytes and nitric oxide secretion in the lungs of live porcine respiratory and reproductive syndrome virus vaccinated pigs.

Journal Article Viral Immunol · February 2013 Porcine respiratory and reproductive syndrome (PRRS) is an economically important disease of pigs worldwide. Currently used PRRSV vaccines provide incomplete protection. Recently, we identified Mycobacterium tuberculosis whole cell lysate (Mtb WCL) as a po ... Full text Link to item Cite

Mucosal vaccines to prevent porcine reproductive and respiratory syndrome: a new perspective.

Journal Article Anim Health Res Rev · June 2012 Porcine reproductive and respiratory syndrome (PRRS) is an economically important infectious disease of swine. Constant emergence of variant strains of PRRS virus (PPRSV) and virus-mediated immune evasion followed by viral persistence result in increased i ... Full text Link to item Cite

Evaluation of immune responses to porcine reproductive and respiratory syndrome virus in pigs during early stage of infection under farm conditions.

Journal Article Virol J · February 16, 2012 BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) causes chronic, economically devastating disease in pigs of all ages. Frequent mutations in the viral genome result in viruses with immune escape mutants. Irrespective of regular vacci ... Full text Link to item Cite

Biodegradable nanoparticle-entrapped vaccine induces cross-protective immune response against a virulent heterologous respiratory viral infection in pigs.

Journal Article PLoS One · 2012 Biodegradable nanoparticle-based vaccine development research is unexplored in large animals and humans. In this study, we illustrated the efficacy of nanoparticle-entrapped UV-killed virus vaccine against an economically important respiratory viral diseas ... Full text Link to item Cite

Intranasal delivery of an adjuvanted modified live porcine reproductive and respiratory syndrome virus vaccine reduces ROS production.

Journal Article Viral Immunol · December 2011 Reactive oxygen species (ROS) are produced predominantly by phagocytic cells in response to microbial infections. When produced at optimal levels ROS have potent antimicrobial properties. However, excessive production of ROS induces apoptosis/necrosis of i ... Full text Link to item Cite

Cross-protective immunity to porcine reproductive and respiratory syndrome virus by intranasal delivery of a live virus vaccine with a potent adjuvant.

Journal Article Vaccine · May 23, 2011 Porcine reproductive and respiratory syndrome (PRRS) is an immunosuppressive chronic respiratory viral disease of pigs that is responsible for major economic losses to the swine industry worldwide. The efficacy of parenteral administration of widely used m ... Full text Link to item Cite

Intranasal delivery of whole cell lysate of Mycobacterium tuberculosis induces protective immune responses to a modified live porcine reproductive and respiratory syndrome virus vaccine in pigs.

Journal Article Vaccine · May 23, 2011 Porcine reproductive and respiratory syndrome (PRRS) is an economically important disease to pork producers worldwide. Commercially, both live and killed PRRSV vaccines are available to control PRRS, but they are not always successful. Based on the results ... Full text Link to item Cite

Functional invariant NKT cells in pig lungs regulate the airway hyperreactivity: a potential animal model.

Journal Article J Clin Immunol · April 2011 Important roles played by invariant natural killer T (iNKT) cells in asthma pathogenesis have been demonstrated. We identified functional iNKT cells and CD1d molecules in pig lungs. Pig iNKT cells cultured in the presence of α-GalCer proliferated and secre ... Full text Link to item Cite

Swine influenza H1N1 virus induces acute inflammatory immune responses in pig lungs: a potential animal model for human H1N1 influenza virus.

Journal Article J Virol · November 2010 Pigs are capable of generating reassortant influenza viruses of pandemic potential, as both the avian and mammalian influenza viruses can infect pig epithelial cells in the respiratory tract. The source of the current influenza pandemic is H1N1 influenza A ... Full text Link to item Cite