Abstract：
:Previously, we documented the role of the programmed death-1 (PD-1, also known as PDCD1) pathway in macrophage apoptosis and the downregulation of this signaling during infection by the intra-macrophage parasite Leishmania donovani However, we also found that, during the late phase of infection, PD-1 expression was significantly increased without activating host cell apoptosis; here we show that inhibition of PD-1 led to markedly decreased parasite survival, along with increased production of TNFα, IL-12, reactive oxygen species (ROS) and nitric oxide (NO). Increased PD-1 led to inactivation of AKT proteins resulting in nuclear sequestration of FOXO-1. Transfecting infected cells with constitutively active FOXO-1 (CA-FOXO) led to increased cell death, thereby suggesting that nuclear FOXO-1 might be inactivated. Infection significantly induced the expression of SIRT1, which inactivated FOXO-1 through deacetylation, and its knockdown led to increased apoptosis. SIRT1 knockdown also significantly decreased parasite survival along with increased production of TNFα, ROS and NO. Administration of the SIRT1 inhibitor sirtinol (10 mg/kg body weight) in infected mice decreased spleen parasite burden and a synergistic effect was found with PD-1 inhibitor. Collectively, our study shows that Leishmania utilizes the SIRT1/FOXO-1 axis for differentially regulating PD-1 signaling and, although they are interconnected, both pathways independently contribute to intracellular parasite survival.This article has an associated First Person interview with the first author of the paper.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Roy S,Saha S,Gupta P,Ukil A,Das PKdoi
10.1242/jcs.226274subject
Has Abstractpub_date
2019-05-02 00:00:00issue
9eissn
0021-9533issn
1477-9137pii
jcs.226274journal_volume
132pub_type
杂志文章abstract：:The cytoplasmic pH of growing pollen tubes of Lilium longiflorum Thunb. was measured using the pH-sensitive fluorescent dye 2',7'-bis-(carboxyethyl)-5(6')-carboxyfl uorescein and confocal fluorescence ratio imaging. The average cytoplasmic pH in the clear zone of the pollen tube tip was pH 7.11, and no consistent pH g...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1997-08-01 00:00:00
abstract：:Transcription factor E2F plays an important role in coordinating and integrating early cell cycle progression with the transcription apparatus. It is known that physiological E2F arises when a member of two families of proteins, E2F and DP, interact as E2F/DP heterodimers and that transcriptional activity is regulated...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1997-11-01 00:00:00
abstract：:We have recently shown that leukotriene D(4) (LTD(4)) increases cell survival in intestinal epithelial cells. Here we report and explore the complementary finding that LTD(4) also enhances proliferation in these cells. This proliferative response was approximately half of that induced by epidermal growth factor (EGF) ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2002-05-01 00:00:00
abstract：:In order to study the dynamic behavior of intermediate filament networks in living cells, we have prepared constructs fusing green fluorescent protein to intermediate filament proteins. Vimentin fused to green fluorescent protein labeled the endogenous intermediate filament network. We generated stable SW13 and NIH3T3...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1998-07-01 00:00:00
abstract：:Gp78 (also known as AMFR and RNF45) is an E3 ubiquitin ligase that targets proteins for proteasomal degradation through endoplasmic reticulum (ER)-associated degradation (ERAD). In this study, we showed that gp78-mediated ubiquitylation is initiated in the peripheral ER. Substrate monoubiquitylation and gp78 CUE domai...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.096396
更新日期：2012-04-01 00:00:00
abstract：:Dispersion of neural crest cells and their ultimate regroupment into peripheral ganglia are associated with precisely coordinated regulations both in time and space of the expression and function of cell adhesion receptors. In particular, the disappearance of N-cadherin from the cell surface at the onset of migration ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-12-01 00:00:00
abstract：:The interplay between pathogen-encoded virulence factors and host cell signaling networks is critical for both the establishment and clearance of microbial infections. Yersinia uptake into host cells serves as an in vitro model for exploring how host cells respond to Yersinia adherence. In this study, we provide insig...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2002-07-01 00:00:00
abstract：:Cell fusion plays a well-recognized, physiological role during development. Bone-marrow-derived hematopoietic cells have been shown to fuse with non-hematopoietic cells in a wide variety of tissues. Some organs appear to resolve the changes in ploidy status, generating functional and mitotically-competent events. Howe...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.100123
更新日期：2012-06-15 00:00:00
abstract：:3-Phosphoinositide-dependent protein kinase-1 (PDK1) and phospholipase C (PLC)γ1 are two key enzymes in signal transduction that control several intracellular processes. Despite the fact that PLCγ1 has been investigated for several years, the mechanisms of activation of this enzyme are still not completely clear. Simi...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.100511
更新日期：2012-07-01 00:00:00
abstract：:Coronins are conserved F-actin-binding proteins that are important for motility and actin dynamics. Unlike type I coronins, coronin 2A localizes to stress fibers and some focal adhesions, and is excluded from the leading edge. Depletion of coronin 2A in MTLn3 cells decreases cell motility and turnover of focal adhesio...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.051482
更新日期：2009-09-01 00:00:00
abstract：:E-cadherin is the main cell adhesion molecule of early embryonic and adult epithelial cells. Downregulation of E-cadherin is associated with epithelial-mesenchymal transition during embryonic mesoderm formation and tumor progression. To identify genes whose expression is affected by the loss of E-cadherin, we compared...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-05-01 00:00:00
abstract：:Basonuclin is a zinc finger protein mainly expressed in keratinocytes of the basal layer of epidermis and the outer root sheath of hair follicles. It is also found in abundance in the germ cells of testis and ovary. In cultured keratinocytes, basonuclin is associated with chromatin in all phases of the cell cycle, inc...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1999-09-01 00:00:00
abstract：:Phosphoinositides represent a major class of lipids specifically involved in the organization of signaling cascades, maintenance of the identity of organelles and regulation of multiple intracellular trafficking steps. We previously reported that phosphatidylinositol 5-monophosphate (PI5P), produced by the Shigella fl...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.166314
更新日期：2015-02-15 00:00:00
abstract：:Mitochondrial DNA (mtDNA) replication and transcription are crucial for cell function, but these processes are poorly understood at the single-cell level. We describe a novel fluorescence in situ hybridization protocol, called mTRIP (mitochondrial transcription and replication imaging protocol), that reveals simultane...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.114322
更新日期：2013-02-15 00:00:00
abstract：:Cultured human keratinocytes maintained in 30 microM Ca2+ do not form adherens junctions; however, when the extracellular Ca2+ concentration is raised to 1 mM, adherens junctions form very rapidly. The formation of a junction involves the coordinate organization of intracellular and extracellular components. Cadherins...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-12-01 00:00:00
abstract：:Survivin, a human inhibitor of apoptosis protein (IAP), plays an important role in both cell cycle regulation and inhibition of apoptosis. Survivin is expressed in cells during the G(2)/M phase of the cell cycle, followed by rapid decline of both mRNA and protein levels at the G(1) phase. It has been suggested that ce...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-12-01 00:00:00
abstract：:Many of the cilia- and flagella-specific integral membrane proteins identified to date function to sense the extracellular milieu, and there is considerable interest in defining pathways for targeting such proteins to these sensory organelles. The flagellar glucose transporter of Leishmania mexicana, LmxGT1, is target...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.103028
更新日期：2012-07-15 00:00:00
abstract：:By differential screening of a Xenopus laevis egg cDNA library, we have isolated a 2,111 bp cDNA which corresponds to a maternal mRNA specifically deadenylated after fertilisation. This cDNA, called Eg2, encodes a 407 amino acid protein kinase. The pEg2 sequence shows significant identity with members of a new protein...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1998-03-01 00:00:00
abstract：:Intercellular propagation of signals through connexin32-containing gap junctions is of major importance in physiological processes like nerve activity-dependent glucose mobilization in liver parenchymal cells and enzyme secretion from pancreatic acinar cells. In these cells, as in other organs, more than one type of c...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-04-01 00:00:00
abstract：:Dynamin-related GTPase proteins (DRPs) are main players in membrane remodelling. Conserved DRPs called mitofusins (Mfn1/Mfn2/Fzo1) mediate the fusion of mitochondrial outer membranes (OM). OM fusion depends on self-assembly and GTPase activity of mitofusins as well as on two other proteins, Ugo1 and Mdm30. Here, we de...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.073080
更新日期：2011-04-01 00:00:00
abstract：:In trypanosomes, the flagellum is rooted in the flagellar pocket, a surface micro-domain that is the sole site for endocytosis and exocytosis. By analysis of anterograde or retrograde intraflagellar transport in IFT88RNAi or IFT140RNAi mutant cells, we show that elongation of the new flagellum is not required for flag...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.035626
更新日期：2008-11-15 00:00:00
abstract：:In the presence of sialic acid donors Trypanosoma cruzi acquires up to 10(7) sialic acid residues on its surface, in a reaction catalyzed by its unique trans-sialidase. Most of these sialic acid residues are incorporated into mucin-like glycoproteins. To further understand the biological role of parasite sialylation, ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-04-01 00:00:00
abstract：:In previous work we used immunofluorescent staining with specific antibodies to study the distribution of five desmosomal antigens in the epithelia of different vertebrate animals. We showed that all five antigens were present in all epithelia studied in human, bovine, rat, guinea pig, chick and frog (Rana pipiens) ti...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1984-03-01 00:00:00
abstract：:Quantitative studies on the adhesive properties of transformed cells have yielded inconclusive and sometimes contradictory results. The present investigation has examined adhesive interactions between normal human fibroblasts, established as well as virus-transformed animal cell lines, and human tumour-derived cell li...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1978-10-01 00:00:00
abstract：:Four developmental stages of Rana pipiens, R. pipiens female X R. catesbeiana female, and R. pipiens female X R. esculenta male embryos were fixed in standard electron microscopic fixatives with or without 1% lanthanum nitrate (LN) added. Embryos fixed without LN were embedded and sectioned at 0-5 micrometer and stain...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1977-06-01 00:00:00
abstract：:CENP-C, one of the few known intrinsic proteins of the human centromere, is thought to play structural as well as regulatory roles crucial to proper chromosome segregation and mitotic progression. To further define the functions of CENP-C throughout the cell cycle we have used the yeast interaction trap to identify pr...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1998-07-30 00:00:00
abstract：:The development of the phosphorylase-glycogen complex was studied in cells of the myogenic line L6 at different stages of differentiation. Our results indicate that the complex is already present in mononucleated myoblasts. However, several features of the complex observed in the myoblasts, such as the total amount of...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1977-08-01 00:00:00
abstract：:Centaurin-alpha(1) is a phosphatidylinositol 3,4,5-trisphosphate binding protein as well as a GTPase activating protein (GAP) for the ADP-ribosylation factor (ARF) family of small GTPases. To further understand its cellular function, we screened a rat brain cDNA library using centaurin-alpha(1) as bait to identify cen...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.02369
更新日期：2005-06-01 00:00:00
abstract：:Programmed cell death comprises several subtypes, as revealed by electron microscopy. Apoptosis or type I programmed cell death is characterized by condensation of cytoplasm and preservation of organelles, essentially without autophagic degradation. Autophagic cell death or type II programmed cell death exhibits exten...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-04-01 00:00:00
abstract：:ARVCF is a novel Armadillo repeat domain protein that is closely related to the catenin p120(ctn). Using new ARVCF monoclonal antibodies, we have found that ARVCF associates with E-cadherin and competes with p120 for interaction with the E-cadherin juxtamembrane domain. ARVCF also localized to the nucleus in some cell...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-04-01 00:00:00
