scholarly journals Cannabinoid control of gingival immune activation in chronically SIV-infected rhesus macaques involves modulation of the indoleamine-2,3-dioxygenase-1 pathway and salivary microbiome

EBioMedicine ◽  
2022 ◽  
Vol 75 ◽  
pp. 103769
Author(s):  
Marina McDew-White ◽  
Eunhee Lee ◽  
Xavier Alvarez ◽  
Karol Sestak ◽  
Binhua J Ling ◽  
...  
Keyword(s):  
Immune Activation ◽  
Rhesus Macaques ◽  
Indoleamine 2,3 Dioxygenase

scholarly journals Urinary suPAR: a non-invasive biomarker of infection and tissue inflammation for use in studies of large free-ranging mammals

2020 ◽  
Vol 7 (2) ◽  
pp. 191825 ◽  
Author(s):  
James P. Higham ◽  
Christiane Stahl-Hennig ◽  
Michael Heistermann
Keyword(s):  
Immune Activation ◽  
Rhesus Macaques ◽  
Soluble Form ◽  
Surgical Trauma ◽  
Large Mammals ◽  
Urokinase Plasminogen Activator Receptor ◽  
Different Temperatures ◽  
Processing And Storage ◽  
Cellular Immune ◽  
Free Ranging

Studies of large free-ranging mammals incorporating physiological measurements typically require the collection of urine or faecal samples, due to ethical and practical concerns over trapping or darting animals. However, there is a dearth of validated biomarkers of immune activation and inflammation that can be measured non-invasively. We here evaluate the utility of urinary measurements of the soluble form of the urokinase plasminogen activator receptor (suPAR), for use as a health marker in studies of wild large mammals. We investigate how urinary suPAR concentrations change in response to viral infection and surgical trauma (inflammation), comparing it to the measurement of a marker of cellular immune activation, urinary neopterin (uNEO), in captive rhesus macaques. We then test the field utility of urinary suPAR, assessing the effects of soil and faecal contamination, sunlight, storage at different temperatures, freeze–thaw cycles, and lyophilization. We find that suPAR concentrations rise markedly in response to both infection and surgery-associated inflammation, unlike uNEO concentrations, which only rise in response to the former. Our field validation demonstrates that urinary suPAR is reasonably robust to many of the issues associated with field collection, sample processing, and storage, as long as samples can be stored in a freezer. Urinary suPAR is thus a promising biomarker applicable for monitoring various aspects of health in wild primates and potentially also other large mammals.

scholarly journals Differential CD4+ T-Lymphocyte Apoptosis and Bystander T-Cell Activation in Rhesus Macaques and Sooty Mangabeys during Acute Simian Immunodeficiency Virus Infection

2008 ◽  
Vol 83 (2) ◽  
pp. 572-583 ◽  
Author(s):  
Mareike Meythaler ◽  
Amanda Martinot ◽  
Zichun Wang ◽  
Sarah Pryputniewicz ◽  
Melissa Kasheta ◽  
...  
Keyword(s):  
Immune Response ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Immune Activation ◽  
Rhesus Macaques ◽  
Lymphocyte Apoptosis ◽  
Immunodeficiency Virus ◽  
Sooty Mangabeys ◽  
Siv Infection ◽  
Species Specific

ABSTRACT In contrast to pathogenic lentiviral infections, chronic simian immunodeficiency virus (SIV) infection in its natural host is characterized by a lack of increased immune activation and apoptosis. To determine whether these differences are species specific and predicted by the early host response to SIV in primary infection, we longitudinally examined T-lymphocyte apoptosis, immune activation, and the SIV-specific cellular immune response in experimentally infected rhesus macaques (RM) and sooty mangabeys (SM) with controlled or uncontrolled SIV infection. SIVsmE041, a primary SIVsm isolate, reproduced set-point viremia levels of natural SIV infection in SM but was controlled in RM, while SIVmac239 replicated to high levels in RM. Following SIV infection, increased CD8+ T-lymphocyte apoptosis, temporally coinciding with onset of SIV-specific cellular immunity, and elevated plasma Th1 cytokine and gamma interferon-induced chemokine levels were common to both SM and RM. Different from SM, SIV-infected RM showed a significantly higher frequency of peripheral blood activated CD8+ T lymphocytes despite comparable magnitude of the SIV-specific gamma interferon enzyme-linked immunospot response. Furthermore, an increase in CD4+ and CD4−CD8− T-lymphocyte apoptosis and plasma tumor necrosis factor-related apoptosis-inducing ligand were observed only in RM and occurred in both controlled SIVsmE041 and uncontrolled SIVmac239 infection. These data suggest that the “excess” activated T lymphocytes in RM soon after SIV infection are predominantly of non-virus-specific bystander origin. Thus, species-specific differences in the early innate immune response appear to be an important factor contributing to differential immune activation in natural and nonnatural hosts of SIV infection.

scholarly journals Reduced Chronic Lymphocyte Activation following Interferon Alpha Blockade during the Acute Phase of Simian Immunodeficiency Virus Infection in Rhesus Macaques

2018 ◽  
Vol 92 (9) ◽  
Author(s):  
Diane Carnathan ◽  
Benton Lawson ◽  
Joana Yu ◽  
Kalpana Patel ◽  
James M. Billingsley ◽  
...  
Keyword(s):  
Interferon Alpha ◽  
Immune Activation ◽  
Rhesus Macaques ◽  
Lymphocyte Activation ◽  
High Dose ◽  
Type I ◽  
Chronic Immune Activation ◽  
Viral Loads ◽  
Immunodeficiency Virus ◽  
Siv Infection

ABSTRACT Pathogenic human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection of humans and rhesus macaques (RMs) induces persistently high production of type I interferon (IFN-I), which is thought to contribute to disease progression. To elucidate the specific role of interferon alpha (IFN-α) in SIV pathogenesis, 12 RMs were treated prior to intravenous (i.v.) SIV mac239 infection with a high or a low dose of an antibody (AGS-009) that neutralizes most IFN-α subtypes and were compared with six mock-infused, SIV-infected controls. Plasma viremia was measured postinfection to assess the effect of IFN-α blockade on virus replication, and peripheral blood and lymphoid tissue samples were analyzed by immunophenotypic staining. Consistent with the known antiviral effect of IFN-I, high-dose AGS-009 treatment induced a modest increase in acute-phase viral loads versus controls. Four out of 6 RMs receiving a high dose of AGS-009 also experienced an early decline in CD4 + T cell counts that was associated with progression to AIDS. Interestingly, 50% of the animals treated with AGS-009 (6/12) developed AIDS within 1 year of infection compared with 17% (1/6) of untreated controls. Finally, blockade of IFN-α decreased the levels of activated CD4 + and CD8 + T cells, as well as B cells, as measured by PD-1 and/or Ki67 expression. The lower levels of activated lymphocytes in IFN-α-blockaded animals supports the hypothesis that IFN-α signaling contributes to lymphocyte activation during SIV infection and suggests that this signaling pathway is involved in controlling virus replication during acute infection. The potential anti-inflammatory effect of IFN-α blockade should be explored as a strategy to reduce immune activation in HIV-infected individuals. IMPORTANCE Interferon alpha (IFN-α) is a member of a family of molecules (type I interferons) that prevent or limit virus infections in mammals. However, IFN-α production may contribute to the chronic immune activation that is thought to be the primary cause of immune decline and AIDS in HIV-infected patients. The study presented here attempts to understand the contribution of IFN-α to the natural history and progression of SIV infection of rhesus macaques, the primary nonhuman primate model system for testing hypotheses about HIV infection in humans. Here, we show that blockade of IFN-α action promotes lower chronic immune activation but higher early viral loads, with a trend toward faster disease progression. This study has significant implications for new treatments designed to impact the type I interferon system.

scholarly journals Activation of Innate Immunity in Healthy Macaca mulatta Macaques by a Single Subcutaneous Dose of GMP CpG 7909: Safety Data and Interferon-Inducible Protein-10 Kinetics for Humans and Macaques

2007 ◽  
Vol 15 (2) ◽  
pp. 221-226 ◽  
Author(s):  
V. Ann Stewart ◽  
Shannon McGrath ◽  
Arthur M. Krieg ◽  
Noelle S. Larson ◽  
Evelina Angov ◽  
...  
Keyword(s):  
Rhesus Macaque ◽  
Immune Activation ◽  
Rhesus Macaques ◽  
Innate Immune ◽  
Suitable Model ◽  
Clinical Grade ◽  
Single Subcutaneous Dose ◽  
Subcutaneous Dose ◽  
Inducible Protein ◽  
Interferon Inducible Protein

ABSTRACT Following a demonstration that mouse-optimized cytosine-guanosine dinucleotide (CpG) oligodeoxynucleotides stimulated innate immune protection against intracellular pathogens, we tested the ability of CpG 7909, a primate-optimized Toll-like receptor 9 (TLR9) agonist, to stimulate rhesus macaques to produce interferon-inducible protein-10 (IP-10), a biomarker of immune activation. This study was performed prior to a similar trial with humans in order to facilitate the development of CpG 7909 as an immunomodulator for biodefense. A single subcutaneous dose of clinical-grade CpG 7909 was given to four groups of healthy adult rhesus macaques (0-mg dose [n = 5], 0.75-mg dose [n = 9], 1.5-mg dose [n = 9], and 3.0-mg dose [n = 9]). Directed physical examination findings, clinical laboratory values, and serum IP-10 concentrations were collected at scheduled intervals for 28 days. All three dose levels of CpG 7909 were safe and not associated with significant clinical or laboratory abnormality. The time to peak serum IP-10 concentration was 1.0 days at the 0.75-mg dose and 0.5 days at the 1.5- and 3.0-mg doses. A dose-dependent response was observed for the magnitude and duration of IP-10 concentrations, which remained significantly above baseline for 3 days for the 3.0-mg and 1.5-mg dose groups but above baseline for only 2 days for the 0.75-mg dose group. There were no nonresponders to CpG 7909. These rhesus macaque safety and IP-10 response data closely parallel a subsequent phase 1 human study of subcutaneously administered CpG 7909. A single dose of clinical-grade CpG 7909 induced a rapid, sustained IP-10 response, a biomarker for activation of the innate immune system. Given the similar susceptibilities of humans and rhesus macaques to infectious diseases, the rhesus macaque appears to be a suitable model to evaluate the potential of CpG 7909-mediated innate immune activation to protect humans against pathogens.

scholarly journals Lipopolysaccharide Increases Immune Activation and Alters T Cell Homeostasis in SHIVB’WHUChronically Infected Chinese Rhesus Macaque

2015 ◽  
Vol 2015 ◽  
pp. 1-13
Author(s):  
Gao-Hong Zhang ◽  
Run-Dong Wu ◽  
Hong-Yi Zheng ◽  
Xiao-Liang Zhang ◽  
Ming-Xu Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Activation ◽  
Rhesus Macaques ◽  
Effector Memory ◽  
Memory Cells ◽  
T Cell Homeostasis ◽  
Programmed Cell Death 1 ◽  
Effector Memory Cells ◽  
Lymphocyte Homeostasis ◽  
Chinese Rhesus Macaques

Immune activation plays a significant role in the disease progression of HIV. Microbial products, especially bacterial lipopolysaccharide (LPS), contribute to immune activation. Increasing evidence indicates that T lymphocyte homeostasis disruptions are associated with immune activation. However, the mechanism by which LPS affects disruption of immune response is still not fully understood. Chronically SHIVB’WHU-infected Chinese rhesus macaques received 50 μg/kg body weight LPS in this study. LPS administration affected the virus/host equilibrium by elevating the levels of viral replication and activating T lymphocytes. LPS induced upregulation of CD8+naïve T cells and downregulated the number of CD4+and CD8+T effector memory cells. The downregulated effector memory cells are associated with a lower frequency of monofunctional and polyfunctional cells, and an upregulated programmed cell death-1 (PD-1) expression on CD4+and CD8+T cells was observed in monkeys after LPS stimulation. Our data provide new insights into the function of LPS in the immune activation in SHIV/HIV infection.

scholarly journals No reactivation of attenuated immunodeficiency viruses in rhesus macaques after vaccinia virus-induced immune activation.

1997 ◽  
Vol 78 (10) ◽  
pp. 2523-2528 ◽  
Author(s):  
U Dittmer ◽  
G Hunsmann ◽  
C Stahl-Hennig ◽  
T Nisslein ◽  
A Meyerhans
Keyword(s):  
Vaccinia Virus ◽  
Immune Activation ◽  
Rhesus Macaques

scholarly journals Plasmacytoid dendritic cells are recruited to the colorectum and contribute to immune activation during pathogenic SIV infection in rhesus macaques

Blood ◽  
2011 ◽  
Vol 118 (10) ◽  
pp. 2763-2773 ◽  
Author(s):  
Suefen Kwa ◽  
Sunil Kannanganat ◽  
Pragati Nigam ◽  
Mariam Siddiqui ◽  
Ravi Dyavar Shetty ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Activation ◽  
Rhesus Macaques ◽  
Virus Infections ◽  
Natural Hosts ◽  
Siv Infection ◽  
Gastrointestinal Tissue ◽  
The Impact

AbstractIn SIV/HIV infection, the gastrointestinal tissue dominates as an important site because of the impact of massive mucosal CD4 depletion and immune activation-induced tissue pathology. Unlike AIDS-susceptible rhesus macaques, natural hosts do not progress to AIDS and resolve immune activation earlier. Here, we examine the role of dendritic cells (DCs) in mediating immune activation and disease progression. We demonstrate that plasmacytoid DCs (pDCs) in the blood up-regulate β7-integrin and are rapidly recruited to the colorectum after a pathogenic SIV infection in rhesus macaques. These pDCs were capable of producing proinflammatory cytokines and primed a T cytotoxic 1 response in vitro. Consistent with the up-regulation of β7-integrin on pDCs, in vivo blockade of α4β7-integrin dampened pDC recruitment to the colorectum and resulted in reduced immune activation. The up-regulation of β7-integrin expression on pDCs in the blood also was observed in HIV-infected humans but not in chronically SIV-infected sooty mangabeys that show low levels of immune activation. Our results uncover a new mechanism by which pDCs influence immune activation in colorectal tissue after pathogenic immunodeficiency virus infections.

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