Infection with the intracellular protozoan parasite Theileria parva induces constitutively high levels of NF-kappa B in bovine T lymphocytes

1989 ◽  
Vol 9 (11) ◽  
pp. 4677-4686
Author(s):  
V Ivanov ◽  
B Stein ◽  
I Baumann ◽  
D A Dobbelaere ◽  
P Herrlich ◽  
...  
Keyword(s):  
T Cells ◽  
Phorbol Esters ◽  
Protozoan Parasite ◽  
Lymphoproliferative Disease ◽  
Host Cells ◽  
Specific Gene ◽  
Theileria Parva ◽  
Nf Kappa B ◽  
Intracellular Protozoan Parasite

The intracellular protozoan parasite Theileria parva causes a lymphoproliferative disease of T cells in cattle and uncontrolled lymphocyte proliferation in culture. We have identified and characterized in infected cells the transcriptional activator, NF-kappa B, whose recognition motifs have been identified in several gene enhancers important for lymphocyte-specific gene expression. NF-kappa B is normally constitutively activated in nuclear extracts derived from B cells and can be induced in T cells and nonlymphoid cells by phorbol esters. Theileria-infected lymphocytes contained constitutively high levels of activated NF-kappa B in nuclear fractions and inactive NF-kappa B in cytoplasmic fractions. The inactive cytoplasmic precursor could be activated by treatment of extracts with deoxycholate, which was shown previously to dissociate NF-kappa B from an inhibitor, I kappa B. Treatment of lymphocyte extracts with 3 mM GTP stimulated NF-kappa B binding to its recognition motif in vitro, thereby distinguishing it from a related nuclear factor, H2-TF1. Selective killing of the parasite, which left the host cells intact, resulted in a rapid loss of NF-kappa B from the nuclear fractions and a slower loss from the cytoplasmic fractions. In parasitized cells, NF-kappa B could not be further stimulated by treatment with 12-O-tetradecanoylphorbol-13-acetate whereas in cells treated to remove the parasite, this compound stimulated elevated levels of NF-kappa B. We propose that high levels of activated NF-kappa B are maintained by the presence of the parasite in infected T cells. Similarly, we propose that the high levels of inactive cytoplasmic precursor are a result of increased synthesis due to the presence of the parasite.

scholarly journals Infection with the intracellular protozoan parasite Theileria parva induces constitutively high levels of NF-kappa B in bovine T lymphocytes.

1989 ◽  
Vol 9 (11) ◽  
pp. 4677-4686 ◽  
Author(s):  
V Ivanov ◽  
B Stein ◽  
I Baumann ◽  
D A Dobbelaere ◽  
P Herrlich ◽  
...  
Keyword(s):  
T Cells ◽  
Phorbol Esters ◽  
Protozoan Parasite ◽  
Lymphoproliferative Disease ◽  
Host Cells ◽  
Specific Gene ◽  
Theileria Parva ◽  
Nf Kappa B ◽  
Intracellular Protozoan Parasite

The intracellular protozoan parasite Theileria parva causes a lymphoproliferative disease of T cells in cattle and uncontrolled lymphocyte proliferation in culture. We have identified and characterized in infected cells the transcriptional activator, NF-kappa B, whose recognition motifs have been identified in several gene enhancers important for lymphocyte-specific gene expression. NF-kappa B is normally constitutively activated in nuclear extracts derived from B cells and can be induced in T cells and nonlymphoid cells by phorbol esters. Theileria-infected lymphocytes contained constitutively high levels of activated NF-kappa B in nuclear fractions and inactive NF-kappa B in cytoplasmic fractions. The inactive cytoplasmic precursor could be activated by treatment of extracts with deoxycholate, which was shown previously to dissociate NF-kappa B from an inhibitor, I kappa B. Treatment of lymphocyte extracts with 3 mM GTP stimulated NF-kappa B binding to its recognition motif in vitro, thereby distinguishing it from a related nuclear factor, H2-TF1. Selective killing of the parasite, which left the host cells intact, resulted in a rapid loss of NF-kappa B from the nuclear fractions and a slower loss from the cytoplasmic fractions. In parasitized cells, NF-kappa B could not be further stimulated by treatment with 12-O-tetradecanoylphorbol-13-acetate whereas in cells treated to remove the parasite, this compound stimulated elevated levels of NF-kappa B. We propose that high levels of activated NF-kappa B are maintained by the presence of the parasite in infected T cells. Similarly, we propose that the high levels of inactive cytoplasmic precursor are a result of increased synthesis due to the presence of the parasite.

scholarly journals Transcription factor Etv6 regulates functional differentiation of cross-presenting classical dendritic cells

2018 ◽  
Vol 215 (9) ◽  
pp. 2265-2278 ◽  
Author(s):  
Colleen M. Lau ◽  
Ioanna Tiniakou ◽  
Oriana A. Perez ◽  
Margaret E. Kirkling ◽  
George S. Yap ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Transcription Factor ◽  
T Cell ◽  
Cd8 T Cells ◽  
Functional Differentiation ◽  
Specific Gene ◽  
Hematopoietic Stem

An IRF8-dependent subset of conventional dendritic cells (cDCs), termed cDC1, effectively cross-primes CD8+ T cells and facilitates tumor-specific T cell responses. Etv6 is an ETS family transcription factor that controls hematopoietic stem and progenitor cell (HSPC) function and thrombopoiesis. We report that like HSPCs, cDCs express Etv6, but not its antagonist, ETS1, whereas interferon-producing plasmacytoid dendritic cells (pDCs) express both factors. Deletion of Etv6 in the bone marrow impaired the generation of cDC1-like cells in vitro and abolished the expression of signature marker CD8α on cDC1 in vivo. Moreover, Etv6-deficient primary cDC1 showed a partial reduction of cDC-specific and cDC1-specific gene expression and chromatin signatures and an aberrant up-regulation of pDC-specific signatures. Accordingly, DC-specific Etv6 deletion impaired CD8+ T cell cross-priming and the generation of tumor antigen–specific CD8+ T cells. Thus, Etv6 optimizes the resolution of cDC1 and pDC expression programs and the functional fitness of cDC1, thereby facilitating T cell cross-priming and tumor-specific responses.

scholarly journals Very late antigen 4-dependent adhesion and costimulation of resting human T cells by the bacterial beta 1 integrin ligand invasin.

1993 ◽  
Vol 177 (1) ◽  
pp. 207-212 ◽  
Author(s):  
E Ennis ◽  
R R Isberg ◽  
Y Shimizu
Keyword(s):  
T Cells ◽  
T Cell ◽  
Adhesion Molecules ◽  
Cd4 T Cells ◽  
Yersinia Pseudotuberculosis ◽  
Biological Properties ◽  
Host Cells ◽  
Late Antigen ◽  
Integrin Ligand

Bacteria and viruses often use the normal biological properties of host adhesion molecules to infect relevant host cells. The outer membrane bacterial protein invasin mediates the attachment of Yersinia pseudotuberculosis to human cells. In vitro studies have shown that four members of the very late antigen (VLA) integrin family of adhesion molecules, VLA-3, VLA-4, VLA-5, and VLA-6, can bind to invasin. Since CD4+ T cells express and use these integrins, we have investigated the interaction of CD4+ T cells with purified invasin. Although VLA integrin-mediated adhesion of T cells to other ligands such as fibronectin does not occur at high levels unless the T cells are activated, resting T cells bind strongly to purified invasin. The binding of resting T cells to invasin requires metabolic activity and an intact cytoskeleton. Although CD4+ T cells express VLA-3, VLA-4, VLA-5, and VLA-6, monoclonal antibody (mAb) blocking studies implicate only VLA-4 as a T cell invasin receptor. Like other integrin ligands, invasin can facilitate T cell proliferative responses induced by a CD3-specific mAb. These results suggest that the nature of the integrin ligand is a critical additional factor that regulates T cell integrin activity, and that direct interactions of T cells with bacterial pathogens such as Yersinia may be relevant to host immune responses to bacterial infection.

scholarly journals The ketolide antibiotics HMR 3647 and HMR 3004 are active against Toxoplasma gondii in vitro and in murine models of infection.

1997 ◽  
Vol 41 (10) ◽  
pp. 2137-2140 ◽  
Author(s):  
F G Araujo ◽  
A A Khan ◽  
T L Slifer ◽  
A Bryskier ◽  
J S Remington
Keyword(s):  
Toxoplasma Gondii ◽  
Protozoan Parasite ◽  
Host Cells ◽  
Resistant Bacteria ◽  
New Class ◽  
Human Foreskin Fibroblasts ◽  
Significant Toxicity ◽  
Different Strains

Ketolides are a new class of macrolide antibiotics that have been shown to be active against a variety of bacteria including macrolide-resistant bacteria and mycobacteria. We examined two ketolides, HMR 3647 and HMR 3004, for their in vitro and in vivo activities against the protozoan parasite Toxoplasma gondii. In vitro, both ketolides at concentrations as low as 0.05 microg/ml markedly inhibited replication of tachyzoites of the RH strain within human foreskin fibroblasts. HMR 3004 demonstrated some toxicity for host cells after they were exposed to 5 microg of the drug per ml for 72 h. In contrast, HMR 3647 did not show any significant toxicity even at concentrations as high as 25 microg/ml. In vivo, both ketolides provided remarkable protection against death in mice lethally infected intraperitoneally with tachyzoites of the RH strain or orally with tissue cysts of the C56 strain of T. gondii. A dosage of 100 mg of HMR 3647 per kg of body weight per day administered for 10 days protected 50% of mice infected with tachyzoites. The same dosage of HMR 3004 protected 100% of the mice. In mice infected with cysts, a dosage of 30 mg of HMR 3647 per kg per day protected 100% of the mice, whereas a dosage of 40 mg of HMR 3004 per kg per day protected 75% of the mice. These results demonstrate that HMR 3647 and HMR 3004 possess excellent activities against two different strains of T. gondii and may be useful for the treatment of toxoplasmosis in humans.

scholarly journals The Immune Regulatory Function of Lymphoproliferative Double Negative T Cells In Vitro and In Vivo

2002 ◽  
Vol 196 (2) ◽  
pp. 261-267 ◽  
Author(s):  
Megan S. Ford ◽  
Kevin J. Young ◽  
Zhuxu Zhang ◽  
Pamela S. Ohashi ◽  
Li Zhang
Keyword(s):  
T Cells ◽  
Fas Ligand ◽  
Lymphoproliferative Disease ◽  
Receptor Expression ◽  
Third Party ◽  
Regulatory Function ◽  
Double Negative ◽  
Double Negative T Cells

Lymphoproliferative (lpr) mice, which lack functional Fas receptor expression and develop autoimmune lymphoproliferative disease, have an accumulation of T cell receptor-αβ+CD4−CD8− (double negative T cells [DNTC]) in the periphery. The function of the accumulating DNTC is not clear. In this study we demonstrate that B6/lpr DNTC can dose dependently kill syngeneic CD8+ and CD4+ T cells from wild-type B6 mice through Fas/Fas ligand interactions in vitro. We also demonstrate that B6/lpr DNTC that are activated and expand in vivo are able to specifically down-regulate allogeneic immune responses mediated by syngeneic Fas+CD4+ and CD8+ T cells in vivo. B6/lpr DNTC that have been preactivated in vivo by infusion of either class I– (bm1) or class II– (bm12) mismatched allogeneic lymphocytes are able to specifically enhance the survival of bm1 or bm12, but not third-party skin allografts when adoptively transferred into naive B6+/+ mice. These findings clearly demonstrate that B6/lpr DNTC have a potent immune regulatory function in vitro and in vivo. They also provide new insights into the mechanisms involved in the development of autoimmune disease in lpr mice.

Modulation of enzymatic activity of Src-family kinases in bovine T cells transformed by Theileria parva

Parasitology ◽  
1998 ◽  
Vol 117 (2) ◽  
pp. 107-115 ◽  
Author(s):  
C. FICH ◽  
U. KLAUENBERG ◽  
B. FLEISCHER ◽  
B. M. BRÖKER
Keyword(s):  
T Cells ◽  
Enzymatic Activity ◽  
Cell Lines ◽  
Essential Role ◽  
Critical Role ◽  
Src Family Kinases ◽  
Theileria Parva ◽  
Transformation Mechanism ◽  
Transformed Cell Lines

After infection with sporozoites of the protozoon Theileria parva (Tp) bovine T cells are readily transformed to permanent growth in vivo and in vitro. Their transformed state depends on the constant presence of the parasite but membrane signals remain important. Non-receptor tyrosine kinases play a critical role in the transduction of membrane signals in haematopoietic cells. We have investigated Src-family kinases in bovine T cells transformed by Tp. The T cell receptor-associated tyrosine kinase p60fyn had high activity in all cell lines tested. In addition, weak phosphorylation of 2 novel bands was observed associated with Fyn. In contrast to Fyn, enzymatic activity of p56lck, which in T cells has an essential role in signalling, was low. Furthermore, 1 of 3 Tp transformed cell lines was completely devoid of p56lck indicating that the enzyme is not necessary for the Tp dependent growth of the T cells. In addition to p60fyn and p56lck weak enzymatic activity of 1 splice variant of p53/56lyn was observed after infection of T cells with Tp. These data show that growth transformation by Tp influences kinase activity in bovine T cells. However, they also prove that p56lck does not play an essential role in the transformation mechanism.

scholarly journals Co-Administration of Anticancer Candidate MK-2206 Enhances the Efficacy of BCG Vaccine Against Mycobacterium tuberculosis in Mice and Guinea Pigs

2021 ◽  
Vol 12 ◽  
Author(s):  
Rania Bouzeyen ◽  
Saurabh Chugh ◽  
Tannu Priya Gosain ◽  
Mohamed-Ridha Barbouche ◽  
Meriam Haoues ◽  
...  
Keyword(s):  
T Cells ◽  
Guinea Pigs ◽  
Protective Efficacy ◽  
T Cell Response ◽  
Host Cells ◽  
Mice Model ◽  
Akt Inhibitor ◽  
Induction Of Apoptosis ◽  
Induced Immunity

The failure of M. bovis BCG to induce long-term protection has been endowed to its inability to escape the phagolysosome, leading to mild activation of CD8+ mediated T cell response. Induction of apoptosis in host cells plays an important role in potentiating dendritic cells-mediated priming of CD8+ T cells, a process defined as “cross-priming.” Moreover, IL-10 secretion by infected cells has been reported to hamper BCG-induced immunity against Tuberculosis (TB). Previously, we have reported that apoptosis of BCG-infected macrophages and inhibition of IL-10 secretion is FOXO3 dependent, a transcription factor negatively regulated by the pro-survival activated threonine kinase, Akt. We speculate that FOXO3-mediated induction of apoptosis and abrogation of IL-10 secretion along with M. bovis BCG immunization might enhance the protection imparted by BCG. Here, we have assessed whether co-administration of a known anti-cancer Akt inhibitor, MK-2206, enhances the protective efficacy of M. bovis BCG in mice model of infection. We observed that in vitro MK-2206 treatment resulted in FOXO3 activation, enhanced BCG-induced apoptosis of macrophages and inhibition of IL-10 secretion. Co-administration of M. bovis BCG along with MK-2206 also increased apoptosis of antigen-presenting cells in draining lymph nodes of immunized mice. Further, MK-2206 administration improved BCG-induced CD4+ and CD8+ effector T cells responses and its ability to induce both effector and central memory T cells. Finally, we show that co-administration of MK-2206 enhanced the protection imparted by M. bovis BCG against Mtb in aerosol infected mice and guinea pigs. Taken together, we provide evidence that MK-2206-mediated activation of FOXO3 potentiates BCG-induced immunity and imparts protection against Mtb through enhanced innate immune response.

Infection of mammalian cells with Theileria species

Parasitology ◽  
1983 ◽  
Vol 86 (2) ◽  
pp. 243-254 ◽  
Author(s):  
D. A. Stagg ◽  
A. S. Young ◽  
B. L. Leitch ◽  
J. G. Grootenhuis ◽  
T. T. Dolan
Keyword(s):  
Host Range ◽  
Mammalian Cells ◽  
Mammalian Species ◽  
Rhipicephalus Appendiculatus ◽  
Host Cells ◽  
Transformed Cells ◽  
Theileria Parva ◽  
African Buffalo

SUMMARYExperiments were carried out to determine the susceptibility of mammalian cells to infection with different species of Theileria in vitro. Sporozoites of Theileria parva (parva), Theileria parva (lawrencei) and Theileria taurotragi were isolated from Rhipicephalus appendiculatus ticks by grinding infected ticks in medium, filtering the suspension and concentrating by centrifugation. The sporozoites were used in attempts to infect in vitro peripheral blood leucocytes harvested from 16 different mammalian species which included 12 species of Bovidae from 6 different sub-families. The technique was shown to be both sensitive and reproducible. The sporozoites of T. parva (parva) infected and transformed cells from 2 species of the sub-family Bovinae, the two cattle types and African buffalo. Theileria parva (lawrencei) infected and transformed cells from the two cattle types, African buffalo and Defassa waterbuck. Theileria taurotragi sporozoites infected in vitro cells from 11 different species of Bovidae which were members of 6 sub-families; Bovinae, Tragelaphinae, Reduncinae, Alcelaphinae, Antilopinae and Caprinae. Transformed lymphoblastoid cell lines were established from 7 of the species infected. Sporozoite attachment and infection was not observed with non-susceptible bovid host cells, nor were any of the non-bovid leucocytes infected by the parasites. The host range observed in this study corresponded to the known host range in vivo.

Morphological characterization ofCryptosporidium parvumlife-cycle stages in anin vitromodel system

Parasitology ◽  
2009 ◽  
Vol 137 (1) ◽  
pp. 13-26 ◽  
Author(s):  
H. BOROWSKI ◽  
R. C. A. THOMPSON ◽  
T. ARMSTRONG ◽  
P. L. CLODE
Keyword(s):  
Electron Microscopy ◽  
Life Cycle ◽  
Protozoan Parasite ◽  
Morphological Characterization ◽  
Host Cells ◽  
Epithelial Cell Line ◽  
Life Cycle Stages ◽  
Complete Life Cycle ◽  
Behavioural Characteristics

SUMMARYCryptosporidium parvumis a zoonotic protozoan parasite that mainly affects the ileum of humans and livestock, with the potential to cause severe enteric disease. We describe the complete life cycle ofC. parvumin anin vitrosystem. Infected cultures of the human ileocecal epithelial cell line (HCT-8) were observed over time using electron microscopy. Additional data are presented on the morphology, development and behavioural characteristics of the different life-cycle stages as well as determining their time of occurrence after inoculation. Numerous stages ofC. parvumand their behaviour have been visualized and morphologically characterized for the first time using scanning electron microscopy. Further, parasite-host interactions and the effect ofC. parvumon host cells were also visualized. An improved understanding of the parasite's biology, proliferation and interactions with host cells will aid in the development of treatments for the disease.

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