scholarly journals Visualizing Cytokine-Secreting Cells In Situ in the Rhesus Macaque Model of Chronic Gut Inflammation

2005 ◽  
Vol 12 (1) ◽  
pp. 192-197 ◽  
Author(s):  
Geeta Ramesh ◽  
Xavier Alvarez ◽  
Juan T. Borda ◽  
Pyone P. Aye ◽  
Andrew A. Lackner ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Lamina Propria ◽  
Rhesus Macaques ◽  
Epifluorescence Microscopy ◽  
Lymphoid Tissues ◽  
Primate Model ◽  
Necrosis Factor Alpha ◽  
Macaque Model ◽  
Tnf Α

ABSTRACT Cytokine-producing cells in gut-associated lymphoid tissues of rhesus macaques with chronic enterocolitis were studied. The confocal microscopy technique that we developed enables simultaneous in situ visualization of multiple extra- and/or intracellular antigens at a resolution higher than that allowed by light or epifluorescence microscopy. The presence of interleukin-6 (IL-6)-, tumor necrosis factor alpha (TNF-α)-, and IL-1-α-producing cells was focally intense in the colon lamina propria of the affected animals. The IL-1-α-producing cells were T lymphocytes (CD3+), while the TNF-α-producing cells were both macrophages (CD68+/HAM56+/LN5+) and T lymphocytes (CD3+). The IL-6-producing cells within the colon consisted of T lymphocytes and macrophages. The amount of IL-6-producing cells seen in macaques with enterocolitis was significantly higher (P < 0.001) than that seen in the healthy control animal, while TNF-α- and IL-1-α-producing cells were seen only in macaques with enterocolitis. Most of the T lymphocytes that produced cytokines were detected in the lamina propria, while the macrophages were most prominent in highly inflamed regions of the lamina propria. Taken together, our findings indicate that there might be immunological similarity between chronic enterocolitis of rhesus macaques and humans, suggesting the potential use of the nonhuman primate model for the validation of novel therapies.

In situ cytokine gene expression in early stage of virulent Newcastle disease in chickens

2021 ◽  
pp. 030098582110459
Author(s):  
Corrie Brown ◽  
Jian Zhang ◽  
Mary Pantin-Jackwood ◽  
Kiril Dimitrov ◽  
Helena Lage Ferreira ◽  
...  
Keyword(s):  
B Cells ◽  
Newcastle Disease ◽  
Early Stage ◽  
Severe Disease ◽  
Cytokine Gene Expression ◽  
Lymphoid Tissues ◽  
Tnf Α ◽  
Virulent Newcastle Disease Virus ◽  
Ifn Γ

Selected lymphoid and reproductive tissues were examined from groups of 3-week-old chickens and 62-week-old hens that were inoculated choanally and conjunctivally with 106 EID50 of a virulent Newcastle disease virus (NDV) isolate from the California 2018–2020 outbreak, and euthanized at 1, 2, and 3 days postinfection. In the 3-week-old chickens, immunohistochemistry for NDV and for T and B cell lymphocytes, as well as in situ hybridization for IL-1β, IL-6, IFN-γ, and TNF-α revealed extensive expression of IL-1β and IL-6 in lymphoid tissues, often coinciding with NDV antigen. IFN-γ was only expressed infrequently in the same lymphoid tissues, and TNF-α was rarely expressed. T-cell populations initially expanded but by day 3 their numbers were below control levels. B cells underwent a similar expansion but remained elevated in some tissues, notably spleen, cecal tonsils, and cloacal bursa. Cytokine expression in the 62-week-old hens was overall lower than in the 3-week-old birds, and there was more prolonged infiltration of both T and B cells in the older birds. The strong pro-inflammatory cytokine response in young chickens is proposed as the reason for more severe disease.

scholarly journals Immunological Responses to the Relapsing Fever SpirocheteBorrelia turicataein Infected Rhesus Macaques: Implications for Pathogenesis and Diagnosis

2019 ◽  
Vol 87 (4) ◽  
Author(s):  
Monica E. Embers ◽  
Aparna Krishnavajhala ◽  
Brittany A. Armstrong ◽  
Michael W. Curtis ◽  
Bapi Pahar ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Rhesus Macaques ◽  
Surface Proteins ◽  
Vaccine Antigen ◽  
Global Public Health ◽  
Relapsing Fever ◽  
Primate Model ◽  
Necrosis Factor Alpha ◽  
Content Type

ABSTRACTThe global public health impact of relapsing fever (RF) spirochetosis is significant, since the pathogens exist on five of seven continents. The hallmark sign of infection is episodic fever and the greatest threat is to the unborn. With the goal of better understanding the specificity of B-cell responses and the role of immune responses in pathogenicity, we infected rhesus macaques withBorrelia turicatae(a new world RF spirochete species) by tick bite and monitored the immune responses generated in response to the pathogen. Specifically, we evaluated inflammatory mediator induction by the pathogen, host antibody responses to specific antigens, and peripheral lymphocyte population dynamics. Our results indicate thatB. turicataeelicits from peripheral blood cells key inflammatory response mediators (interleukin-1β and tumor necrosis factor alpha), which are associated with preterm abortion. Moreover, a global decline in peripheral B-cell populations was observed in all animals at 14 days postinfection. Serological responses were also evaluated to assess the antigenicity of three surface proteins: BipA, BrpA, and Bta112. Interestingly, a distinction was observed between antibodies generated in nonhuman primates and mice. Our results provide support for the nonhuman primate model not only in studies of prenatal pathogenesis but also for diagnostic and vaccine antigen identification and testing.

scholarly journals Flow Cytometric Determination of Cellular Sources and Frequencies of Key Cytokine-Producing Lymphocytes Directed against Recombinant LACK and Soluble Leishmania Antigen in Human Cutaneous Leishmaniasis

2001 ◽  
Vol 69 (5) ◽  
pp. 3232-3239 ◽  
Author(s):  
R. L. A. Bottrel ◽  
W. O. Dutra ◽  
F. A. Martins ◽  
B. Gontijo ◽  
E. Carvalho ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cutaneous Leishmaniasis ◽  
Ex Vivo ◽  
Protozoan Parasite ◽  
Recombinant Antigen ◽  
Interleukin 4 ◽  
Leishmania Braziliensis ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT Leishmaniasis, caused by infection with the protozoan parasiteLeishmania, affects millions of individuals worldwide, causing serious morbidity and mortality. This study directly determined the frequency of cells producing key immunoregulatory cytokines in response to the recombinant antigen Leishmania homolog of receptors for activated kinase C (LACK) and soluble leishmania antigen (SLA), and it determined relative contributions of these antigens to the overall cytokine profile in individuals infected for the first time with Leishmania braziliensis. All individuals presented with the cutaneous clinical form of leishmaniasis and were analyzed for proliferative responses to LACK antigen and SLA, frequency of lymphocyte subpopulations (analyzed ex vivo), and antigen-induced (LACK and SLA) cytokine production at the single-cell level (determined by flow cytometry). The following were determined. (i) The Th1-type response previously seen in patients with cutaneous leishmaniasis is due to gamma interferon (IFN-γ) production by several different sources, listed in order of contribution: CD4+ T lymphocytes, CD4−, CD8− lymphocytes, and CD8+ T lymphocytes. (ii) SLA induced a higher frequency of lymphocytes producing IFN-γ and tumor necrosis factor alpha (TNF-α) than did LACK. (iii) LACK induced an activation of monocyte populations as reflected by an increased percentage of CD14-positive cells. (iv) Neither SLA nor LACK induced detectable frequencies of cells producing interleukin-4 (IL-4) or IL-5. These data demonstrated a multifaceted immune response to SLA in human leishmaniasis involving Th1 CD4+ T lymphocytes (IFN-γ+ and IL-10−/IL-4−), Tc1 CD8+ T cells (IFN-γ+, and IL-10−/IL-4−), and a high frequency of TNF-α-producing lymphocytes. Moreover, it was determined that the recombinant antigen LACK acts as a weak inducer of Th1-type lymphocyte responses compared to SLA.

scholarly journals Tumor Necrosis Factor Alpha-Deficient, but Not Interleukin-6-Deficient, Mice Resist Peripheral Infection with Scrapie

2000 ◽  
Vol 74 (7) ◽  
pp. 3338-3344 ◽  
Author(s):  
Neil A. Mabbott ◽  
Alun Williams ◽  
Christine F. Farquhar ◽  
Manolis Pasparakis ◽  
Giorgos Kollias ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Lymphoid Tissues ◽  
Wild Type ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Scrapie Strain ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT In most peripheral infections of rodents and sheep with scrapie, infectivity is found first in lymphoid tissues and later in the central nervous system (CNS). Cells within the germinal centers (GCs) of the spleen and lymph nodes are important sites of extraneural replication, from which infection is likely to spread to the CNS along peripheral nerves. Here, using immunodeficient mice, we investigate the identity of the cells in the spleen that are important for disease propagation. Despite possessing functional T and B lymphocytes, tumor necrosis factor alpha-deficient (TNF-α−/−) mice lack GCs and follicular dendritic cell (FDC) networks in lymphoid tissues. In contrast, lymphoid tissues of interleukin-6-deficient (IL-6−/−) mice possess FDC networks but have impaired GCs. When the CNSs of TNF-α−/−, IL-6−/−, and wild-type mice were directly challenged with the ME7 scrapie strain, 100% of the mice were susceptible, developing disease after closely similar incubation periods. However, when challenged peripherally (intraperitoneally), most TNF-α−/− mice failed to develop scrapie up to 503 days postinjection. All wild-type and IL-6−/− mice succumbed to disease approximately 300 days after the peripheral challenge. High levels of scrapie infection and the disease-specific isomer of the prion protein, PrPSc, were detectable in spleens from challenged wild-type and IL-6−/− mice but not from TNF-α−/−mice. Histopathological analysis of spleen tissue demonstrated heavy PrP accumulations in direct association with FDCs in challenged wild-type and IL-6−/− mice. No PrPScaccumulation was detected in spleens from TNF-α−/−mice. We conclude that, for the ME7 scrapie strain, mature FDCs are critical for replication in lymphoid tissues and that in their absence, neuroinvasion following peripheral challenge is impaired.

scholarly journals Administration of an Anti-CD8 Monoclonal Antibody Interferes with the Clearance of Chimeric Simian/Human Immunodeficiency Virus during Primary Infections of Rhesus Macaques

1998 ◽  
Vol 72 (1) ◽  
pp. 164-169 ◽  
Author(s):  
Tetsuro Matano ◽  
Riri Shibata ◽  
Christine Siemon ◽  
Mark Connors ◽  
H. Clifford Lane ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Human Immunodeficiency Virus ◽  
T Lymphocytes ◽  
Acute Phase ◽  
Peripheral Blood ◽  
Rhesus Macaques ◽  
Lymphoid Tissues ◽  
Virus Infections ◽  
Cd4 Cells ◽  
Immunodeficiency Virus

ABSTRACT Parenteral administration of a mouse anti-human CD8 monoclonal antibody (MAb) to rhesus macaques resulted in a transient depletion of CD8+ cells in both the peripheral blood and lymphoid tissues. When administered during primary chimeric simian/human immunodeficiency virus infections, the CD8 MAb caused marked elevations of plasma and cell-associated virus levels in both the peripheral blood and lymphoid tissues and led to prolonged depletion of CD4 cells. Taken together, these results directly demonstrate that CD8+ T lymphocytes are actively involved in controlling the acute phase of primate lentivirus infections.

scholarly journals Human T-Cell Lymphotropic Virus Type 1-Infected T Lymphocytes Impair Catabolism and Uptake of Glutamate by Astrocytes via Tax-1 and Tumor Necrosis Factor Alpha

2000 ◽  
Vol 74 (14) ◽  
pp. 6433-6441 ◽  
Author(s):  
Raphaël Szymocha ◽  
Hideo Akaoka ◽  
Magali Dutuit ◽  
Christophe Malcus ◽  
Marianne Didier-Bazes ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Human T Cell ◽  
Tnf Α ◽  
Factor Alpha ◽  
Transient Contact ◽  
Necrosis Factor

ABSTRACT Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of a chronic progressive myelopathy called tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). In this disease, lesions of the central nervous system (CNS) are associated with perivascular infiltration by lymphocytes. We and others have hypothesized that these T lymphocytes infiltrating the CNS may play a prominent role in TSP/HAM. Here, we show that transient contact of human or rat astrocytes with T lymphocytes chronically infected by HTLV-1 impairs some of the major functions of brain astrocytes. Uptake of extracellular glutamate by astrocytes was significantly decreased after transient contact with infected T cells, while the expression of the glial transporters GLAST and GLT-1 was decreased. In two-compartment cultures avoiding direct cell-to-cell contact, similar results were obtained, suggesting possible involvement of soluble factors, such as cytokines and the viral protein Tax-1. Recombinant Tax-1 and tumor necrosis factor alpha (TNF-α) decreased glutamate uptake by astrocytes. Tax-1 probably acts by inducing TNF-α, as the effect of Tax-1 was abolished by anti-TNF-α antibody. The expression of glutamate-catabolizing enzymes in astrocytes was increased for glutamine synthetase and decreased for glutamate dehydrogenase, the magnitudes of these effects being correlated with the level of Tax-1 transcripts. In conclusion, Tax-1 and cytokines produced by HTLV-1-infected T cells impair the ability of astrocytes to manage the steady-state level of glutamate, which in turn may affect neuronal and oligodendrocytic functions and survival.

scholarly journals Human Brucellosis Is Characterized by an Intense Th1 Profile Associated with a Defective Monocyte Function

2010 ◽  
Vol 78 (7) ◽  
pp. 3272-3279 ◽  
Author(s):  
Manuel Rodríguez-Zapata ◽  
Marlene J. Matías ◽  
Alfredo Prieto ◽  
Marco A. Jonde ◽  
Jorge Monserrat ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Peripheral Blood ◽  
Phagocytic Activity ◽  
Human Brucellosis ◽  
Blood Monocytes ◽  
Phagocytic Cells ◽  
Necrosis Factor Alpha ◽  
Th1 Response ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT In animal models, a defective Th1 response appears to be critical in the pathogenesis of brucellosis, but the Th1 response in human brucellosis patients remains partially undefined. Peripheral blood from 24 brucellosis patients was studied before and 45 days after antibiotherapy. Twenty-four sex- and age-matched healthy donors were analyzed in parallel. Significantly increased levels of interleukin 1β (IL-1β), IL-2, IL-4, IL-6, IL-12p40, gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), but not of IL-10, in serum and/or significantly increased percentages of samples with detectable levels of these cytokines, measured by enzyme-linked immunosorbent assays (ELISA), were found for untreated brucellosis patients, but these levels were reduced and/or normalized after treatment. Flow cytometry studies showed that the intracytoplasmic expression of IFN-γ, IL-2, and TNF-α, but not that of IL-4, by phorbol myristate-activated CD4+ CD3+ and CD8+ CD3+ T lymphocytes was significantly increased in untreated brucellosis patients and was also partially normalized after antibiotherapy. The percentage of phagocytic cells, the mean phagocytic activity per cell, and the phagocytic indices for monocytes at baseline were defective and had only partially reverted at follow-up. T lymphocytes from untreated brucellosis patients are activated in vivo and show Th1 cytokine production polarization, with strikingly high serum IFN-γ levels. In spite of this Th1 environment, we found deficient effector phagocytic activity in peripheral blood monocytes.

scholarly journals Development of a Rotavirus-Shedding Model in Rhesus Macaques, Using a Homologous Wild-Type Rotavirus of a New P Genotype

2005 ◽  
Vol 79 (2) ◽  
pp. 944-954 ◽  
Author(s):  
Monica M. McNeal ◽  
Karol Sestak ◽  
Anthony H.-C. Choi ◽  
Mitali Basu ◽  
Michael J. Cole ◽  
...  
Keyword(s):  
Rhesus Macaques ◽  
Nucleotide Sequence Analysis ◽  
Primate Research ◽  
Wild Type ◽  
Primate Model ◽  
Challenge Virus ◽  
Model Studies ◽  
Macaque Model ◽  
Clinically Normal ◽  
New Genotype

ABSTRACT Although there are several reports on rotavirus inoculation of nonhuman primates, no reliable model exists. Therefore, this study was designed to develop a rhesus macaque model for rotavirus studies. The goals were to obtain a wild-type macaque rotavirus and evaluate it as a challenge virus for model studies. Once rotavirus was shown to be endemic within the macaque colony at the Tulane National Primate Research Center, stool specimens were collected from juvenile animals (2.6 to 5.9 months of age) without evidence of previous rotavirus infection and examined for rotavirus antigen. Six of 10 animals shed rotavirus during the 10-week collection period, and the electropherotypes of all isolates were identical to each other but distinct from those of prototype simian rotaviruses. These viruses were characterized as serotype G3 and subgroup 1, properties typical of many animal rotaviruses, including simian strains. Nucleotide sequence analysis of the VP4 gene was performed with a culture-grown isolate from the stool of one animal, designated the TUCH strain. Based on both genotypic and phylogenetic comparisons between TUCH VP4 and cognate proteins of representatives of the reported 22 P genotypes, the TUCH virus belongs to a new genotype, P[23]. A pool of wild-type TUCH was prepared and intragastrically administered to eight cesarean section-derived, specific-pathogen-free macaques 14 to 42 days of age. All animals were kept in a biocontainment level 2 facility. Although no diarrhea was observed and the animals remained clinically normal, all animals shed large quantities of rotavirus antigen in their feces after inoculation, which resolved by the end of the 14-day observation period. Therefore, TUCH infection of macaques provides a useful nonhuman primate model for studies on rotavirus protection.

scholarly journals Macaques with Rapid Disease Progression and Simian Immunodeficiency Virus Encephalitis Have a Unique Cytokine Profile in Peripheral Lymphoid Tissues

2001 ◽  
Vol 75 (9) ◽  
pp. 4448-4452 ◽  
Author(s):  
Marlene S. Orandle ◽  
Kenneth C. Williams ◽  
Andrew G. MacLean ◽  
Susan V. Westmoreland ◽  
Andrew A. Lackner
Keyword(s):  
Disease Progression ◽  
Simian Immunodeficiency Virus ◽  
Cytokine Profile ◽  
Cytokine Gene Expression ◽  
Lymphoid Tissues ◽  
Necrosis Factor Alpha ◽  
Viral Loads ◽  
Macaque Model ◽  
Immunodeficiency Virus ◽  
Ifn Γ

ABSTRACT The influence of host cytokine response on viral load, disease progression, and neurologic lesions was investigated in the simian immunodeficiency virus (SIV)-infected macaque model of AIDS. Cytokine gene expression (interleukin-1β [IL-1β], IL-2, IL-6, IL-10, gamma interferon [IFN-γ], and tumor necrosis factor alpha [TNF-α]) and viral loads were evaluated by semiquantitative reverse transcription-PCR in lymph nodes of 5 control animals and 28 animals infected with SIVmac251 at the terminal stages of AIDS. Infected animals showed higher expression of IFN-γ, IL-6, and IL-10 mRNAs compared with controls. Levels of all cytokines were comparable between animals with rapid (survival, <200 days) or slow/normal (survival, >200 days) disease progression. However, among rapid progressors, the eight animals with SIV encephalitis had a unique cytokine profile (increased IL-2, IL-6, and IFN-γ) that was associated with higher viral loads. These observations provide evidence that host cytokine responses may influence SIV neuropathogenesis independent of disease progression.

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