Elizabeth Didier

Elizabeth Didier
Tulane University | TU · Tulane National Primate Research Center

Ph.D.

About

167
Publications
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7,928
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Publications

Publications (167)
Article
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Background Late-stage human immunodeficiency virus (HIV) infection is typically characterized by low CD4 + T-cell count. We previously showed that profound changes in the monocyte turnover (MTO) rate in rhesus macaques infected by the simian immunodeficiency virus (SIV) outperforms declining CD4 + T-cell counts in predicting rapid health decline as...
Article
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Background Melioidosis is a disease caused by the bacterium Burkholderia pseudomallei, infecting humans and non-human primates (NHP) through contaminated soil or water. World-wide there are an estimated 165,000 human melioidosis cases each year, but recordings of NHP cases are sporadic. Clinical detection of melioidosis in humans is primarily by cu...
Chapter
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Destruction of CD4+ T cells is a primary cause of immunodeficiency in Human Immunodeficiency Virus (HIV)-infected humans and Simian Immunodeficiency Virus (SIV)-infected rhesus macaques. Tissue macrophages, however, also contribute to AIDS pathogenesis. Studies on rhesus macaque lung revealed the presence of at least two types of macrophages compri...
Article
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Aging is characterized by a loss of bone marrow hematopoietic tissue, systemic chronic inflammation, and higher susceptibility to infectious and noninfectious diseases. We previously reported the tightly regulated kinetics and massive daily production of neutrophils during homeostasis in adult rhesus macaques aged 3 to 19 yr (equivalent to approxim...
Article
Objectives: CD4+ T-cell decline and increasing virus levels are considered hallmarks of HIV/AIDS pathogenesis but we previously demonstrated in rhesus macaques that tissue macrophage destruction by SIV infection associated with increased monocyte turnover also appear to impact pathogenesis. It remains unclear, however, which factors best predict o...
Article
Lax phenotypic characterization of these morphologically distinct pericytes has delayed our understanding of their role in neurological disorders. We herein establish markers which uniquely distinguish different subpopulations of human brain microvascular pericytes and characterize them independently from cerebrovascular smooth muscle cells. Furthe...
Article
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Background: Clinical measurements commonly used to evaluate overall health of laboratory animals including complete blood count, serum chemistry, weight, and immunophenotyping, differ with respect to age, development, and environment. This report provides comprehensive clinical and immunological reference ranges for pediatric rhesus macaques over t...
Article
Cardiovascular disease is a major cause of morbidity in aging and in HIV-infected individuals despite efficacy of cART, and furthermore, is associated with macrophage activation and inflammation. Nonhuman primates simulate human disease, and we previously reported that distinct macrophage populations play different roles in the pathogenesis of dise...
Article
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A geropathology grading platform (GGP) for assessing age-related lesions has been established and validated for in inbred strain of mice. Because nonhuman primates (NHPs) share significant similarities in aging and spontaneous chronic diseases with humans, they provide excellent translational value for correlating histopathology with biological and...
Article
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The development of chronic inflammation, called inflammaging, contributes to the pathogenesis of age-related diseases. Although it is known that both B and T lymphocyte compartments of the adaptive immune system deteriorate with advancing age, the impact of aging on immune functions of Th17-type CD161-expressing innate immune cells and their role i...
Article
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Rhesus macaques are physiologically similar to humans and, thus, have served as useful animal models of human diseases including cardiovascular disease. The purpose of this study was to characterize the distribution, composition, and phenotype of macrophages in heart tissues of very young (fetus: 0.5 years, n = 6), young adult (2–12 years, n = 12),...
Article
Aging is characterized with a loss of hematopoietic tissue in bone marrow, systemic chronic inflammation, and higher susceptibility to infectious diseases. We previously showed the tightly regulated kinetics and massive daily production of neutrophils during homeostasis in rhesus macaques aged 3 to 19 years old. Here we extended that study to furth...
Article
Obligately intracellular microsporidia regulate their host cell life cycles, including apoptosis, but this has not been evaluated in phagocytic host cells such as macrophages that can facilitate infection but also can be activated to kill microsporidia. We examined two biologically dissimilar human-infecting microsporidia species, Encephalitozoon c...
Article
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Dextrans have been used extensively as medical therapies and labeling agents in biomedical research to investigate theblood-brain barrier and CSF flow and absorption. Adverse effects from dextrans include anaphylactic reaction and dilation ofthe cerebral ventricles due to administration into the subarachnoid space. This retrospective study describe...
Article
Neutrophils, basophils, and monocytes are continuously produced in bone marrow via myelopoiesis, circulate in blood, and are eventually removed from circulation to maintain homeostasis. To quantitate the kinetics of myeloid cell movement during homeostasis, we applied 5-bromo-2'-deoxyuridine pulse labeling in healthy rhesus macaques (Macaca mulatta...
Article
Background: Tuberculosis (TB) and human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) profoundly affect the immune system and synergistically accelerate disease progression. It is believed that CD4+ T-cell depletion by HIV is the major cause of immunodeficiency and reactivation of latent TB. Previous studies demonstrated...
Article
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Monocytes/macrophages are a diverse group of cells that act as first responders in innate immunity and then as mediators for adaptive immunity to help clear infections. In performing these functions, however, the macrophage inflammatory responses can also contribute to pathogenesis. Various monocyte and tissue macrophage subsets have been associate...
Article
Infant humans and rhesus macaques infected with the human or simian immunodeficiency virus (HIV or SIV), respectively, express higher viral loads and progress more rapidly to AIDS than infected adults. Activated memory CD4 T cells in intestinal tissues are major primary target cells for SIV/HIV infection, and massive depletion of these cells is con...
Article
Full-text available
Infant humans and rhesus macaques infected with the human or simian immunodeficiency virus (HIV or SIV), respectively, express higher viral loads and progress more rapidly to AIDS than infected adults. Activated memory CD4⁺ T cells in intestinal tissues are major primary target cells for SIV/HIV infection, and massive depletion of these cells is co...
Article
BACKGROUND HIV/SIV establishes lifelong infection by integrating proviral DNA into the genome of susceptible long-lived immune cells. In order to eliminate the virus, cellular reservoirs must be removed. Long-lived macrophages are permissible to SIV infection and replication. Given recent publications describing adipose as a tissue reservoir for HI...
Article
Myeloid cells are continuously produced via bone marrow hematopoiesis and then cleared from the circulation to maintain homeostasis. To better understand the kinetics of such cell movement, we applied in vivo BrdU pulse-chase labeling and flow cytometry analysis to follow the kinetics of cell division during homeostasis of each subset of myeloid ce...
Article
In SIV-infected adult Macaca mulatta, increases in monocyte turnover indicates death of short-lived tissue macrophages and predicts SAIDS. Increased turnover also correlates with infection, not death, of long-lived tissue macrophages. Higher baseline monocyte turnover is measured in neonates, and faster disease progression. Our data shows increase...
Article
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Intensification of food production has the potential to drive increased disease prevalence in food plants and animals. Microsporidia are diversely distributed, opportunistic, and density-dependent parasites infecting hosts from almost all known animal taxa. They are frequent in highly managed aquatic and terrestrial hosts, many of which are vulnera...
Article
Incidence of newly-acquired HIV infections in persons over age 50 is increasing, from 13% in 2006 to 21% in 2013. Advanced age corresponds with lower 12-month survival and ART is contraindicated with the simultaneous use of many chronic disease medications. To address the need for age-specific interventions, we are studying aged rhesus macaques (RM...
Article
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Aging is the biological process of declining physiologic function associated with increasing mortality rate during advancing age. Humans and higher nonhuman primates exhibit unusually longer average life spans as compared with mammals of similar body mass. Furthermore, the population of humans worldwide is growing older as a result of improvements...
Article
The systematically difficult task of diagnosing Lyme disease can be simplified by sensitive and specific laboratory tests. The currently recommended two-tier test for serology is highly specific, but falls short in sensitivity, especially in the early acute phase. We previously examined serially collected serum samples from Borrelia burgdorferi -in...
Article
Full-text available
Intensification of food production has the potential to drive increased disease prevalence in food plants and animals. Microsporidia are diversely distributed, opportunistic, and density-dependent parasites infecting hosts from almost all known animal taxa. They are frequent in highly managed aquatic and terrestrial hosts, many of which are vulnera...
Article
Full-text available
To our knowledge, this study demonstrates for the first time that the AIDS virus differentially impacts two distinct subsets of lung macrophages. The predominant macrophages harvested by bronchoalveolar lavage (BAL), alveolar macrophages (AMs), are routinely used in studies on human lung macrophages, are long-lived cells, and exhibit low turnover....
Article
Several enteric microsporidia species have been detected in humans and other vertebrates and their identifications at the genotype level are currently being elucidated. As advanced methods, reagents, and disposal kits for detecting and identifying pathogens become commercially available, it is important to test them in settings other than in labora...
Article
Full-text available
Monocyte and dendritic cell (DC) development was evaluated using in vivo BrdU pulse-chase analyses in rhesus macaques, and phenotype analyses of these cells in blood also were assessed by immunostaining and flow cytometry for comparisons among rhesus, cynomolgus, and pigtail macaques, as well as African green monkeys and humans. The nonhuman primat...
Article
Declining CD4+ T cells during HIV infection contributes to immunodeficiency, but we recently reported that increasing monocyte turnover better predicted onset of terminal disease progression to AIDS in SIV-infected rhesus macaques. Here we describe the kinetics of SIV infection on distinct lung macrophage subsets and on monocyte/macrophage turnover...
Article
Accelerated aging occurs in HIV-infected persons HIV, despite ART, as seen by earlier onset of chronic inflammatory diseases and HIV-associated non-AIDS (HANA) conditions than in non-HIV-infected individuals. In the rhesus macaque SIV model, we reported earlier that increasing monocyte turnover associated with tissue macrophage death predicted onse...
Article
We recently reported that increasing blood monocyte turnover that was associated with tissue macrophage death better predicts terminal disease progression in adult SIV-infected macaques than does declining CD4(+) T cell levels. To understand better mechanisms of pathogenesis, this study relates severity of lung-tissue damage to the ratio, distribut...
Article
We recently reported that increasing blood monocyte turnover that was associated with tissue macrophage death better predicts terminal disease progression in adult SIV-infected macaques than does declining CD4 + T cell levels. To understand better mechanisms of pathogenesis, this study relates severity of lung-tissue damage to the ratio, distributi...
Article
The purpose of this chapter is to review the mammalian models of micro-sporidia that helped predict and contributed to better understanding this infection and ensuing disease in humans. Many microsporidian species detected in humans cause natural or spontaneous infections in other mammals, and knowledge gained from these observations provided insig...
Chapter
This chapter summarizes what is understood about mammalian host immune responses to microsporidia species infecting humans as well as the effects of microsporidia infection on the host immune system. The commonly identified microsporidia in humans belong to the genera Enterocytozoon and Encephalitozoon, and infections typically occur through oral t...
Chapter
The phylum Microsporidia comprises an interesting group of intracellular fungal parasites that infect vertebrate and invertebrate hosts of commercial and medical significance. Microsporidia are unique for their mode of infection, whereby the spore contents are propelled through an inverting polar filament and injected into the host cell. Believed t...
Article
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Alveolar macrophages (AMs) obtained by bronchoalveolar lavage (BAL) are commonly used to study lung macrophage-mediated immune responses. Questions remain, however, about whether AMs fully represent macrophage function in the lung. This study was performed to determine the contribution of interstitial macrophages (IMs) of lung tissue to pulmonary i...
Chapter
This chapter focuses on the clinical manifestations associated with microsporidiosis including overviews on the epidemiology and immune response to these parasites, approaches to diagnose infection, and strategies to treat or prevent infection and disease. Reactivation of infection in infected immune-competent mice administered corticosteroids and...
Article
Quantification of plasma viral load (PVL) is used to monitor disease progression in SIV-infected macaques. This study was aimed at optimizing of performance characteristics of the quantitative PCR (qPCR) PVL assay. The PVL quantification procedure was optimized by inclusion of an exogenous control hepatitis C virus armored RNA (aRNA), a plasma conc...
Article
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Background The microsporidian Encephalitozoon cuniculi possesses one of the most reduced and compacted eukaryotic genomes. Reduction in this intracellular parasite has affected major cellular machinery, including the loss of over fifty core spliceosomal components compared to S. cerevisiae. To identify expression changes throughout the parasite’s l...
Article
The 13th International Workshops on Opportunistic Protists (IWOP-13) was held November 13 to 15, 2014 in Seville, Spain. The objectives of the IWOP meetings are to: (1) Serve as a forum for exchange of new information among active researchers concerning the basic biology, molecular genetics, immunology, biochemistry, pathogenesis, drug development,...
Article
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Background Questions remain about whether inflammation is a cause, consequence, or coincidence of aging. The purpose of this study was to define baseline immunological characteristics from blood to develop a model in rhesus macaques that could be used to address the relationship between inflammation and aging. Hematology, flow cytometry, clinical c...
Article
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Bivalve species with exceptional longevity are newly introduced model systems in biogerontology to test evolutionarily conserved mechanisms of aging. Here, we tested predictions based on the oxidative stress hypothesis of aging using one of the tropical long-lived sessile giant clam species, the smooth giant clam (Tridacna derasa; predicted maximum...
Article
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Background An effective AIDS vaccine remains one of the highest priorities in HIV-research. Our recent study showed that vaccination of rhesus macaques with recombinant simian varicella virus (rSVV) vector – simian immunodeficiency virus (SIV) envelope and gag genes, induced neutralizing antibodies and cellular immune responses to SIV and also sign...
Data
Figure S2. Intracellular cytokine responses measured against SIV-Env and SIV-Gag antigens in Control vaccinated macaques were shown. PBMC were unstimulated (medium control) or stimulated for 6 h with different SIV-Env and/or SIV-Gag peptide pools at 14d post immunization (d14pi), day of challenge (doc) (A & B) and 231d post challenge (pc) time poin...
Data
Full-text available
Figure S1. Intracellular cytokine flow cytometry for IFNγ, TNFα and IL2 responses from a representative rSVV-SIVEnv and rSVV-SIVGag vaccinated rhesus macaque. Cells were gated first on singlets, lymphocytes, followed by live cells and then on CD3+ T-cells and subsequently on CD3+CD4+ and CD3+CD8+ T-cell subsets. The percentages of IFNγ, TNFα and /o...
Article
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Microsporidia comprise a large phylum of obligate intracellular eukaryotes that are fungal-related parasites responsible for widespread disease, and here we address questions about microsporidia biology and evolution. We sequenced three microsporidian genomes from two species, Nematocida parisii and Nematocida sp1, which are natural pathogens of Ca...
Article
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Adjuvants potentiate antigen-specific protective immune responses and can be key elements promoting vaccine effectiveness. We previously reported that the Onchocerca volvulus recombinant protein rOv-ASP-1 can induce activation and maturation of naïve human DCs and therefore could be used as an innate adjuvant to promote balanced Th1 and Th2 respons...
Conference Paper
Full-text available
Background / Purpose: Alveolar macrophages (AM) are important tissue macrophages that play a critical role in the host defense of the respiratory tract. Many opportunistic infections observed in AIDS involve active proliferation of opportunistic pathogens in the lung. We have previously reported that SIV-infected macaques display increased monocy...
Article
Microsporidia have emerged as causes of opportunistic infections associated with diarrhea and wasting in AIDS patients. This review describes recent reports of microsporidiosis in HIV-infected individuals and the growing awareness of microsporidiosis in non-HIV-infected populations. Microsporidia were only rarely recognized as causes of disease in...
Article
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Microsporidia were identified in stool specimens by histochemistry and PCR of 30 (18.9%) of 159 HIV-infected patients presenting to the S. P. Botkin Memorial Clinical Hospital of Infectious Diseases, St. Petersburg, Russia. The higher prevalence of Encephalitozoon intestinalis, in 21 (12.8%) patients, than of Enterocytozoon bieneusi, in 2 patients...
Article
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We assess whether reactive oxygen species production and resistance to oxidative stress might be causally involved in the exceptional longevity exhibited by the ocean quahog Arctica islandica. We tested this hypothesis by comparing reactive oxygen species production, resistance to oxidative stress, antioxidant defenses, and protein damage eliminati...
Article
Immunosenescence is a public health concern. This study was to characterize the peripheral immune system in rhesus macaques of varying ages. Flow cytometry and multiplex cytokine levels were evaluated in blood from 35 monkeys (3.2-20 years old). Linear regression was used to define statistically significant changes (i.e. P<0.05) with age. Significa...
Article
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The genome of the microsporidia Encephalitozoon cuniculi is widely recognized as a model for extreme reduction and compaction. At only 2.9 Mbp, the genome encodes approximately 2,000 densely packed genes and little else. However, the nuclear genome of its sister, Encephalitozoon intestinalis, is even more reduced; at 2.3 Mbp, it represents a 20% re...
Article
Encephalitozoon cuniculi (Phylum Microsporidia) infects a wide range of mammals, and replicates within resting macrophages. Activated macrophages, conversely, inhibit replication and destroy intracellular organisms. These studies were performed to assess mechanisms of innate immune responses expressed by macrophages to control E. cuniculi infection...
Article
Microsporidia are fungi-related, obligate intracellular parasites. Members of the genus, Encephalitozoon, are clinically important as causes of emerging and opportunistic infections associated with diarrhea and systemic disease. E. cuniculi replicates within macrophages and is believed to disseminate via trafficking monocytes/macrophages. Little is...
Article
Full-text available
Microsporidia, particularly Enterocytozoon bieneusi and the Encephalitozoon species, cause diarrhea and systemic disease in humans, and the free-living amebae (FLA) such as Naegleria fowleri and species of Acanthamoeba, cause fatal infections of the central nervous system in humans. Both groups of organisms appear to cause infection via waterborne...
Chapter
Microsporidiosis is a common infection of invertebrates and vertebrates, and has recently been recognized as an emerging and opportunistic infection in humans. Microsporidia infections in immune-competent mammals are often chronic and asymptomatic so that the host survives yet the parasite persists. Immune-deficient hosts such as AIDS patients or a...
Chapter
Microsporidia infect a wide range of invertebrates and vertebrates and were only rarely observed in humans until the mid-1980s when these organisms became recognized as causes of opportunistic infections in persons with acquired immunodeficiency syndrome (AIDS) associated with persistent diarrhoea and wasting. Nowadays, microsporidioses are being i...