scholarly journals 237 Jejunum lymph node transcriptome reveals the importance of genes of phagosome and T cell receptor signalling pathways in Mycobacterium avium ssp. paratuberculosis infection.

2018 ◽  
Vol 96 (suppl_3) ◽  
pp. 22-22
Author(s):  
D Do ◽  
P Dudemaine ◽  
N Bissonnette ◽  
E Ibeagha-Awemu
2021 ◽  
Vol 22 (11) ◽  
pp. 5816
Author(s):  
Suresh Velnati ◽  
Sara Centonze ◽  
Federico Girivetto ◽  
Gianluca Baldanzi

Diacylglycerol kinases are intracellular enzymes that control the balance between the secondary messengers diacylglycerol and phosphatidic acid. DGKα and DGKζ are the prominent isoforms that restrain the intensity of T cell receptor signalling by metabolizing PLCγ generated diacylglycerol. Thus, their activity must be tightly controlled to grant cellular homeostasis and refine immune responses. DGKα is specifically inhibited by strong T cell activating signals to allow for full diacylglycerol signalling which mediates T cell response. In X-linked lymphoproliferative disease 1, deficiency of the adaptor protein SAP results in altered T cell receptor signalling, due in part to persistent DGKα activity. This activity constrains diacylglycerol levels, attenuating downstream pathways such as PKCθ and Ras/MAPK and decreasing T cell restimulation induced cell death. This is a form of apoptosis triggered by prolonged T cell activation that is indeed defective in CD8+ cells of X-linked lymphoproliferative disease type 1 patients. Accordingly, inhibition or downregulation of DGKα activity restores in vitro a correct diacylglycerol dependent signal transduction, cytokines production and restimulation induced apoptosis. In animal disease models, DGKα inhibitors limit CD8+ expansion and immune-mediated tissue damage, suggesting the possibility of using inhibitors of diacylglycerol kinase as a new therapeutic approach.


Nature ◽  
1995 ◽  
Vol 374 (6521) ◽  
pp. 474-476 ◽  
Author(s):  
Klaus-Dieter Fischer ◽  
Antanina Zmuidzinas ◽  
Sandra Gardner ◽  
Mariano Barbacid ◽  
Alan Bernstein ◽  
...  

Brain ◽  
2010 ◽  
Vol 133 (2) ◽  
pp. 375-388 ◽  
Author(s):  
Wei Hu ◽  
Stefan Nessler ◽  
Bernhard Hemmer ◽  
Todd N. Eagar ◽  
Lawrence P. Kane ◽  
...  

Nature ◽  
10.1038/37648 ◽  
1997 ◽  
Vol 390 (6660) ◽  
pp. 629-632 ◽  
Author(s):  
Emanuel F. Petricoin ◽  
Satoshi Ito ◽  
Brandi L. Williams ◽  
Susette Audet ◽  
Louis F. Stancato ◽  
...  

1998 ◽  
Vol 333 (3) ◽  
pp. 615-619 ◽  
Author(s):  
Junji HIROTA ◽  
Masashi BABA ◽  
Mineo MATSUMOTO ◽  
Teiichi FURUICHI ◽  
Kiyoshi TAKATSU ◽  
...  

Stimulation of T-cells via the T-cell receptor (TCR) complex is accompanied by an increase in intracellular Ca2+ concentration ([Ca2+]i). Recently, it was reported that a stable transformant of the human T-cell line, Jurkat, expressing an antisense cDNA construct of inositol 1,4,5-trisphosphate receptor (IP3R) type 1 (IP3R1), failed to demonstrate increased [Ca2+]i or interleukin-2 production after TCR stimulation and was also resistant to apoptotic stimuli. This cell line lacked IP3R1 expression, but expressed the type-2 and -3 receptors, IP3R2 and IP3R3 respectively [Jayaraman, Ondriasova, Ondrias, Harnick and Marks (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 6007–6011, and Jayaraman and Marks (1997) Mol. Cell. Biol. 17, 3005–3012]. The authors concluded that IP3R1 is essential for TCR signalling and suggested that Ca2+ release via IP3R1 is a critical mediator of apoptosis. To establish whether a loss of IP3R1 function in T-cells occurred in vivo and in vitro, we investigated Ca2+ signalling after TCR stimulation and the properties of T-cells using IP3R1-deficient (IP3R1-/-) mice. As IP3R1-/- mice die at weaning, we transplanted bone marrow cells of IP3R1-/- mice into irradiated wild-type mice. Western blot analysis showed that the recipient IP3R1-containing (IP3R1+/+) lymphocytes were replaced by the donor IP3R1-/- lymphocytes after transplantation and that expression of IP3R2 and IP3R3 was unaltered. In contrast with the previous reports, T-cells lacking IP3R1 were able to mobilize Ca2+ from intracellular Ca2+ stores after stimulation via the TCR. We observed no significant differences between IP3R1+/+ and IP3R1-/- T-cells in terms of the number of thymocytes and splenocytes, the proportion of the T-cell phenotype, proliferative response to anti-CD3 monoclonal antibody (mAb) stimulation and cell viability. Therefore IP3R1 is not essential for T-cell development and function.


2015 ◽  
Vol 128 (11) ◽  
pp. 2085-2095 ◽  
Author(s):  
A. L. Furmanski ◽  
A. Barbarulo ◽  
A. Solanki ◽  
C.-I. Lau ◽  
H. Sahni ◽  
...  

2011 ◽  
Vol 32 (12) ◽  
pp. 567-573 ◽  
Author(s):  
Gleb Turchinovich ◽  
Daniel J. Pennington

2012 ◽  
Vol 20 (2) ◽  
pp. 156-165 ◽  
Author(s):  
Chandrashekhar Charavaryamath ◽  
Patricia Gonzalez-Cano ◽  
Patrick Fries ◽  
Susantha Gomis ◽  
Kimberley Doig ◽  
...  

ABSTRACTA lack of appropriate disease models has limited our understanding of the pathogenesis of persistent enteric infections withMycobacterium aviumsubsp.paratuberculosis. A model was developed for the controlled delivery of a defined dose ofM. aviumsubsp.paratuberculosisto surgically isolated ileal segments in newborn calves. The stable intestinal segments enabled the characterization of host responses to persistentM. aviumsubsp.paratuberculosisinfections after a 9-month period, including an analysis of local mucosal immune responses relative to an adjacent uninfected intestinal compartment.M. aviumsubsp.paratuberculosisremained localized at the initial site of intestinal infection and was not detected by PCR in the mesenteric lymph node.M. aviumsubsp.paratuberculosis-specific T cell proliferative responses included both CD4 and γδ T cell receptor (γδTcR) T cell responses in the draining mesenteric lymph node. The levels of CD8+and γδTcR+T cells increased significantly (P< 0.05) in the lamina propria, andM. aviumsubsp.paratuberculosis-specific tumor necrosis factor alpha (TNF-α) and gamma interferon secretion by lamina propria leukocytes was also significantly (P< 0.05) increased. There was a significant (P< 0.05) accumulation of macrophages and dendritic cells (DCs) in the lamina propria, but the expression of mucosal toll-like receptors 1 through 10 was not significantly changed byM. aviumsubsp.paratuberculosisinfection. In conclusion, surgically isolated ileal segments provided a model system for the establishment of a persistent and localized entericM. aviumsubsp.paratuberculosisinfection in cattle and facilitated the analysis ofM. aviumsubsp.paratuberculosis-specific changes in mucosal leukocyte phenotype and function. The accumulation of DC subpopulations in the lamina propria suggests that further investigation of mucosal DCs may provide insight into host responses toM. aviumsubsp.paratuberculosisinfection and improve vaccine strategies to preventM. aviumsubsp.paratuberculosisinfection.


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