bluuebunny/crossref_metadata_2025_split huggingface dataset:
Émeutes : chronique d'une politique-spectacle
Authors: Kyrou Ariel 
Published: August 2009

Résumé Les émeutes en banlieue de novembre 2005 apparaissent avec le recul comme une urgence à s’exprimer mais sans mots. Les blogs ou les doléances d’une association comme AC le feu n’y changent pas grand-chose : la révolte était aphone, dans une société tout entière affectée par la crise du langage. L’opposition ne tient pas, entre des institutions qui parlent et des jeunes des cités qui ne parlent pas. S’il y a bien une panne, c’est celle de la transmission et non de la parole.
A CD26-Controlled Cell Surface Cascade for Regulation of T Cell Motility and Chemokine Signals
Authors: Liu Zhiwen , Christensson Marta , Forslöw Anna , De Meester Ingrid , Sundqvist Karl-Gösta 
Published: August 2009

Abstract
Chemokines are key regulators of cell trafficking, and dipeptidyl peptidase IV/CD26 (CD26) inactivates chemokines. Here we show that the CD26-processed chemokines SDF1α/CXCL12 and RANTES/CCL5, in contrast to a control chemokine not processed by CD26, are potent inducers of cell surface expression of thrombospondin-1 (TSP-1) in T lymphocytes through a CD26-controlled mechanism and that TSP-1 stimulates expression of lipoprotein receptor related protein/CD91. Accordingly, intact TSP-1 and a peptide mimetic of a sequence in TSP-1 were sufficient to stimulate CD91 expression. The chemokine-induced expression of TSP-1 and CD91 was mimicked by inhibitors of CD26 and CXCL12 and CCL5 as well as inhibitors of CD26 stimulated polarized cytoplasmic spreading and migration through TSP-1. Silencing of CD26 using small interfering RNA or Ab-induced modulation of CD26 also increased TSP-1 expression and enhanced cytoplasmic spreading and T cell migration markedly. These results indicate that CD26 is an endogenous inhibitor of T cell motility through inhibition of TSP-1 expression and that chemokines stimulate cell polarity and migration through abrogation of the CD26-dependent inhibition. This suggests that T cell motility is regulated by a cascade of interacting cell surface molecules.
IFN-γ, as Secreted during an Alloresponse, Induces Differentiation of Monocytes into Tolerogenic Dendritic Cells, Resulting in FoxP3+ Regulatory T Cell Promotion
Authors: Eljaafari Assia , Li Yin-Ping , Miossec Pierre 
Published: August 2009

Abstract
IFN-γ has been shown to inhibit monocyte (Mo) differentiation into mature dendritic cells (DC). Because IFN-γ also plays a role in tolerance induction, we asked whether this could be related to generation of tolerogenic DC (Tol-DC). Toward this aim, we cultured Mo with GM-CSF plus IL-4 in the presence or absence of IFN-γ for 6 days and induced their maturation with TNF-α for 2 additional days. We showed that IFN-γ deviated Mo differentiation from mature DC toward Tol-DC. Indeed, IFN-γ-generated DC 1) expressed moderate levels of costimulatory molecules, but high levels of Langerin and CD123 molecules, 2) were maturation resistant, and 3) were unable to efficiently present alloantigen to T cells. More interestingly, naive CD4+ T cells primed with IFN-γ-generated DC expressed FoxP3 mRNA at high levels and exerted regulatory functions upon secondary stimulation with alloantigen. To address whether endogenously secreted IFN-γ mediates a similar effect, we used the alloreaction as a model. We showed that cell-free supernatant harvested from an HLA-mismatched, but not HLA-identical, alloresponse induced differentiation of Mo into Tol-DC able to promote regulatory T cell generation. Moreover, when supplemented with GM-CSF plus IL-4, HLA-mismatched cell-free supernatant inhibited differentiation of Mo into mature DC. Finally, by adding Abs directed against inflammatory cytokines, we demonstrated that IFN-γ plays a preponderant role in this inhibition. In conclusion, our results clearly demonstrate that exogenous or endogenous IFN-γ, as well, induces differentiation of Mo toward Tol-DC, which results in FoxP3+ regulatory T cell promotion.
Resident Dendritic Cells Prevent Postischemic Acute Renal Failure by Help of Single Ig IL-1 Receptor-Related Protein
Authors: Lech Maciej , Avila-Ferrufino Alejandro , Allam Ramanjaneyulu , Segerer Stephan , Khandoga Alexander , Krombach Fritz , Garlanda Cecilia , Mantovani Alberto , Anders Hans-Joachim 
Published: August 2009

Abstract
Ischemia-reperfusion (IR) triggers tissue injury by activating innate immunity, for example, via TLR2 and TLR4. Surprisingly, TLR signaling in intrinsic renal cells predominates in comparison to intrarenal myeloid cells in the postischemic kidney. We hypothesized that immune cell activation is specifically suppressed in the postischemic kidney, for example, by single Ig IL-1-related receptor (SIGIRR). SIGIRR deficiency aggravated postischemic acute renal failure in association with increased renal CXCL2/MIP2, CCL2/MCP-1, and IL-6 mRNA expression 24 h after IR. Consistent with this finding interstitial neutrophil and macrophage counts were increased and tubular cell necrosis was aggravated in Sigirr-deficient vs wild-type IR kidneys. In vivo microscopy revealed increased leukocyte transmigration in the postischemic microvasculature of Sigirr-deficient mice. IL-6 and CXCL2/MIP2 release was much higher in Sigirr-deficient renal myeloid cells but not in Sigirr-deficient tubular epithelial cells after transient hypoxic culture conditions. Renal IR studies with chimeric mice confirmed this finding, as lack of SIGIRR in myeloid cells largely reproduced the phenotype of renal IR injury seen in Sigirr−/− mice. Additionally, clodronate depletion of dendritic cells prevented the aggravated renal failure in Sigirr−/− mice. Thus, loss of function mutations in the SIGIRR gene predispose to acute renal failure because SIGIRR prevents overshooting tissue injury by suppressing the postischemic activation of intrarenal myeloid cells.
CD4+ T Cell Help Has an Epitope-Dependent Impact on CD8+ T Cell Memory Inflation during Murine Cytomegalovirus Infection
Authors: Snyder Christopher M. , Loewendorf Andrea , Bonnett Elizabeth L. , Croft Michael , Benedict Chris A. , Hill Ann B. 
Published: August 2009

Abstract
Murine CMV (MCMV) establishes a systemic, low-level persistent infection resulting in the accumulation of CD8+ T cells specific for a subset of viral epitopes, a process called memory inflation. Although replicating virus is rarely detected in chronically infected C57BL/6 mice, these inflationary cells display a phenotype suggestive of repeated Ag stimulation, and they remain functional. CD4+ T cells have been implicated in maintaining the function and/or number of CD8+ T cells in other chronic infections. Moreover, CD4+ T cells are essential for complete control of MCMV. Thus, we wondered whether CD4+ T cell deficiency would result in impaired MCMV-specific CD8+ T cell responses. Here we show that CD4+ T cell deficiency had an epitope-specific impact on CD8+ T cell memory inflation. Of the three codominant T cell responses during chronic infection, only accumulation of the late-appearing IE3-specific CD8+ T cells was substantially impaired in CD4+ T cell-deficient mice. Moreover, the increased viral activity did not drive increased CD8+ T cell division or substantial dysfunction in any MCMV-specific population that we studied. These data show that CD4+ T cell help is needed for inflation of a response that develops only during chronic infection but is otherwise dispensable for the steady state maintenance and function of MCMV-specific CD8+ T cells.
NADPH Oxidase NOX2 Mediates Rapid Cellular Oxidation following ATP Stimulation of Endotoxin-Primed Macrophages
Authors: Moore Samantha F. , MacKenzie Amanda B. 
Published: August 2009

Abstract
The phagocytic NADPH oxidase (NOX2) plays a fundamental role in host defense and innate immunity. Here we demonstrate that external ATP triggers rapid cellular oxidation inhibited by diphenyleneiodonium in endotoxin-primed J774 macrophages and primary murine bone marrow-derived macrophages. To identify the source of reactive oxygen species (ROS), we compared responses between wild-type and NOX2-deficient macrophages. ATP-mediated ROS production was strongly attenuated in NOX2-deficient macrophages where responses were comparable to inhibition with diphenyleneiodonium. Notably, spatial differences in superoxide anion formation were observed where ROS formation was partially antagonized by extracellular superoxide dismutase in primary bone marrow-derived macrophages but unaffected in J774 macrophages. Loss of NOX2 was not observed to affect ATP-induced cell death. However, ATP-evoked cell death was found to be partially dependent on caspase-1 and cathepsin B activation. In conclusion, NOX2 plays a fundamental role in conferring macrophages with the ability to respond to extracellular ATP stimulation with robust changes in cellular oxidation.
Selective Expansion of HIV-1 Envelope Glycoprotein-Specific B Cell Subsets Recognizing Distinct Structural Elements Following Immunization
Authors: Dosenovic Pia , Chakrabarti Bimal , Soldemo Martina , Douagi Iyadh , Forsell Mattias N. E. , Li Yuxing , Phogat Adhuna , Paulie Staffan , Hoxie James , Wyatt Richard T. , Karlsson Hedestam Gunilla B. 
Published: August 2009

Abstract
The HIV-1 envelope glycoprotein (Env) functional spike has evolved multiple immune evasion strategies, and only a few broadly neutralizing determinants on the assembled spike are accessible to Abs. Serological studies, based upon Ab binding and neutralization activity in vitro, suggest that vaccination with current Env-based immunogens predominantly elicits Abs that bind nonneutralizing or strain-restricted neutralizing epitopes. However, the fractional specificities of the polyclonal mixture of Abs present in serum, especially those directed to conformational Env epitopes, are often difficult to determine. Furthermore, serological analyses do not provide information regarding how repeated Ag inoculation impacts the expansion and maintenance of Env-specific B cell subpopulations. Therefore, we developed a highly sensitive Env-specific B cell ELISPOT system, which allows the enumeration of Ab-secreting cells (ASC) from diverse anatomical compartments directed against different structural determinants of Env. In this study, we use this system to examine the evolution of B cell responses in mice immunized with engineered Env trimers in adjuvant. We demonstrate that the relative proportion of ASC specific for defined structural elements of Env is altered significantly by homologous booster immunizations. This results in the selective expansion of ASC directed against the variable regions of Env. We suggest that the B cell specificity and compartment analysis described in this study are important complements to serological mapping studies for the examination of B cell responses against subspecificities of a variety of immunogens.
Eosinophil Cationic Protein (ECP) Is Processed during Secretion
Authors: Woschnagg Charlotte , Rubin Jenny , Venge Per 
Published: August 2009

Abstract
The eosinophil granulocyte is an inflammatory cell involved in allergic diseases such as asthma and rhinitis. Eosinophil cationic protein (ECP) is a basic and potentially cytotoxic granule protein that is released from the eosinophil upon activation. The aim was to study secretion of molecular variants of ECP from blood eosinophils with the hypothesis that the stored noncytotoxic ECP is altered into cytotoxic species upon release from the cell. Eosinophil granulocytes were purified to &gt;95% from venous blood from birch pollen allergic subjects, with symptoms of rhinitis, and from healthy control subjects during the birch pollen season. The cells were stimulated with IL-5, GM-CSF, or serum-opsonized Sephadex particles. Concentration of ECP in cells or supernatants was measured by means of a fluoroenzyme immunoassay, and ECP heterogeneity was studied using an affinity capture assay with the surface-enhanced laser desorption/ionization-time of flight mass spectrometry technique. Extracts of unstimulated eosinophils contained 10 major ECP variants, with molecular masses ranging from 16.1 to 17.7 kDa. Stimulation with particles mainly induced the secretion of two molecular variants at 16.1 and 16.3 kDa, while cytokine stimulation gave rise to a different secretion profile. ECP variants in the pellet extracts remained unaffected by cell activation. The modifications of secreted ECP were partly explained by differences in N-linked glycosylations. Secretion of ECP from eosinophils involves protein modification. The molecular masses of released ECP have acquired the masses of the cytotoxic species.
Disruption of Th2 Immunity Results in a Gender-Specific Expansion of IL-13 Producing Accessory NK Cells during Helminth Infection
Authors: Hepworth Matthew R. , Grencis Richard K. 
Published: August 2009

Abstract
Host gender has previously been identified as a determining factor in the resolution of Trichuris muris infection in mice lacking IL-4 (IL-4KO BALB/c). Worm expulsion in these mice is delayed, but occurs in females. In this study we were able to demonstrate delayed expulsion occurs at day 26 post infection and is associated with the production of the key Th2-associated cytokine IL-13 by both CD4+ T cells and an auxiliary DX5+ NK cell source, as well as a concurrent reduction in proinflammatory cytokines. NK cell number was comparably increased in both sexes, but NK cells from male mice were found to express higher levels of the chemokine receptor CXCR3. Depletion of CD4+ T cells completely prevented parasite expulsion, whereas loss of NK cells resulted in a mild, but significant delay. Furthermore, IL-18 is a cytokine with the capacity to enhance both Th1 and Th2 responses found to be dispensable for worm expulsion in female mice but was a key factor for the suppression of the Th2 response in male IL-4KO mice. In contrast neutralization of IFN-γ resulted in a complete restoration of typical wild-type BALB/c expulsion kinetics. This study sheds further light on the role of accessory NK cells in supplementing the IL-13-driven immune response when normal Th2 immunity is disrupted, and further identifies host gender as a key factor in determining the generation of “NK cell help”.
A Cell-Intrinsic Role for Mst1 in Regulating Thymocyte Egress
Authors: Dong Yongli , Du Xingrong , Ye Jian , Han Min , Xu Tian , Zhuang Yuan , Tao Wufan 
Published: August 2009

Abstract
The MST1 kinase was recently identified as playing an essential role in the promotion of lymphocyte polarization and adhesion stimulated by chemokines and TCR signaling. However, the physiological relevance of the Mst1 pathway in thymocyte development is not completely understood. In this study, we analyzed the effect of Mst1 disruption on thymocyte development and migration. Mst1-deficient (Mst1−/−) mice displayed an accumulation of mature thymocytes in the thymus, a dramatic reduction of lymphocytes in blood and peripheral lymphoid tissues, and a decrease of homing ability to peripheral lymph nodes. Mst1−/− thymocytes were impaired in chemotactic response to chemokines, such as CCL19, but not to sphingosine-1-phosphate. Further analyses of Mst1−/− mice revealed a severe impairment in the egress of mature T cells from the thymus. T lineage-specific knockout of the Mst1 gene demonstrates a cell-intrinsic role for Mst1 in regulating T cell development. Our study indicates that Mst1 is crucial in controlling lymphocyte chemotaxis and thymocyte emigration.
Secretion and Biological Activity of Short Signal Peptide IL-15 Is Chaperoned by IL-15 Receptor Alpha In Vivo
Authors: Bergamaschi Cristina , Jalah Rashmi , Kulkarni Viraj , Rosati Margherita , Zhang Gen-Mu , Alicea Candido , Zolotukhin Andrei S. , Felber Barbara K. , Pavlakis George N. 
Published: August 2009

Abstract
The two known isoforms of IL-15 contain either a long signal peptide (LSP) or a short signal peptide (SSP), and are produced by alternatively spliced transcripts. It has been proposed that SSP IL-15 remains exclusively intracellular, and its function is unclear. In this study, we show that, similar to LSP IL-15, the SSP IL-15 is stabilized and secreted efficiently upon coexpression of IL-15Rα. Coinjection of SSP IL-15- and IL-15Rα-expressing plasmids into mice resulted in increased plasma levels of bioactive heterodimeric IL-15 and mobilization and expansion of NK and T cells. Therefore, SSP IL-15 is secreted and bioactive when produced as a heterodimer with IL-15Rα in the same cell. The apparent t1/2 of this heterodimer is lower compared with LSP IL-15/IL-15Rα, due to different intracellular processing. Coexpression of both LSP IL-15 and SSP IL-15 in the presence of IL-15Rα results in lower levels of bioactive IL-15, indicating that LSP and SSP IL-15 compete for the binding to IL-15Rα when expressed in the same cell. Because the SSP IL-15 interaction to IL-15Rα leads to a complex with lower apparent stability, SSP IL-15 functions as competitive inhibitor of LSP IL-15. The data suggest that usage of alternative splicing is an additional level of control of IL-15 activity. Expression of both SSP and LSP forms of IL-15 appears to be conserved in many mammals, suggesting that SSP may be important for expressing a form of IL-15 with lower magnitude or duration of biological effects.
Chronic Human Infection with Trypanosoma cruzi Drives CD4+ T Cells to Immune Senescence
Authors: Albareda María Cecilia , Olivera Gabriela Carina , Laucella Susana A. , Alvarez María Gabriela , Fernandez Esteban Rodrigo , Lococo Bruno , Viotti Rodolfo , Tarleton Rick L. , Postan Miriam 
Published: August 2009

Abstract
Previously we found that the frequency of IFN-γ-producing CD8+ T cells specific for Trypanosoma cruzi inversely correlates with disease severity in chronic human Chagas disease along with low levels of IL-2-secreting CD8+ T cells in all clinical stages. This impairment of the parasite-specific T cell responses was associated with phenotypic features of immune senescence of the CD8+ T cell compartment. These data prompted us to address the question of whether the CD4+ T cell compartment also experiences signs of exhaustion. Thus, we performed a functional and phenotypical characterization of T. cruzi-specific and overall CD4+ T cells in chronically infected subjects with different degrees of cardiac dysfunction. The results show an inverse association between disease severity and the frequency of T. cruzi-specific IFN-γ-producing CD4+ T cells. The high expression of CD27 and CD28 with a relative low expression of CD57 found on CD4+IFN-γ+ T cells suggests that the effector T cell pool in chronic T. cruzi infection includes a high proportion of newly recruited T cells, but a low frequency of long-term memory cells. The total CD4+ T cell compartment shows signs of senescence and later stages of differentiation associated with more severe stages of the disease. These findings support the hypothesis that long-term T. cruzi infection in humans might exhaust long-lived memory T cells.
Helicobacter pylori Hp(2–20) Promotes Migration and Proliferation of Gastric Epithelial Cells by Interacting with Formyl Peptide Receptors In Vitro and Accelerates Gastric Mucosal Healing In Vivo
Authors: de Paulis Amato , Prevete Nella , Rossi Francesca W. , Rivellese Felice , Salerno Fiamma , Delfino Gabriele , Liccardo Bianca , Avilla Elvira , Montuori Nunzia , Mascolo Massimo , Staibano Stefania , Melillo Rosa Marina , D'Argenio Giuseppe , Ricci Vittorio , Romano Marco , Marone Gianni 
Published: August 2009

Abstract
Helicobacter pylori-derived peptide RpL1 aa 2–20 (Hp(2–20)) in addition to its antimicrobial action exerts several immunomodulatory effects in eukaryotic cells by interacting with formyl peptide receptors (FPRs). It has recently been shown that activation of FPRs facilitates intestinal epithelial cell restitution. We investigated whether Hp(2–20) induces healing of injured gastric mucosa and assessed the mechanisms underlying any such effect. We investigated the expression of FPRs in two gastric epithelial cell lines (MKN-28 and AGS) at mRNA and protein level. To determine whether FPRs were functional we performed chemotaxis experiments and proliferation assays and studied the Hp(2–20)-activated downstream signaling pathway. The effect of Hp(2–20) on mucosal healing was evaluated in rats after indomethacin-induced injury. Here we show that: (1) FPRs were expressed in both cell lines; (2) Hp(2–20) stimulated migration and proliferation of gastric epithelial cells; (3) this effect was specifically mediated by formyl peptide receptor-like 1 (FPRL1) and FPRL2 and was associated with activation of FPR-related downstream signaling pathways; (4) Hp(2–20) up-regulated the expression and secretion of vascular endothelial growth factor; and (5) Hp(2–20) accelerated healing of rat gastric mucosa after injury brought about by indomethacin at both the macroscopic and microscopic levels. In conclusion, by interacting with FRPL1 and FPRL2, H. pylori-derived Hp(2–20) induces cell migration and proliferation, as well as the expression of vascular endothelial growth factor, thereby promoting gastric mucosal healing. This study provides further evidence of the complexity of the relationship between H. pylori and human gastric mucosa, and it suggests that a bacterial product may be used to heal gastric mucosal injury.
Kinin Danger Signals Proteolytically Released by Gingipain Induce Fimbriae-Specific IFN-γ- and IL-17-Producing T Cells in Mice Infected Intramucosally with Porphyromonas gingivalis
Authors: Monteiro Ana Carolina , Scovino Aline , Raposo Susane , Gaze Vinicius Mussa , Cruz Catia , Svensjö Erik , Narciso Marcelo Sampaio , Colombo Ana Paula , Pesquero João B. , Feres-Filho Eduardo , Nguyen Ky-Anh , Sroka Aneta , Potempa Jan , Scharfstein Julio 
Published: August 2009

Abstract
Porphyromonas gingivalis, a Gram-negative bacterium that causes periodontitis, activates the kinin system via the cysteine protease R-gingipain. Using a model of buccal infection based on P. gingivalis inoculation in the anterior mandibular vestibule, we studied whether kinins released by gingipain may link mucosal inflammation to T cell-dependent immunity through the activation of bradykinin B2 receptors (B2R). Our data show that P. gingivalis W83 (wild type), but not gingipain-deficient mutant or wild-type bacteria pretreated with gingipain inhibitors, elicited buccal edema and gingivitis in BALB/c or C57BL/6 mice. Studies in TLR2−/−, B2R−/−, and neutrophil-depleted C57BL/6 mice revealed that P. gingivalis induced edema through the sequential activation of TLR2/neutrophils, with the initial plasma leakage being amplified by gingipain-dependent release of vasoactive kinins from plasma-borne kininogens. We then used fimbriae (Fim) Ag as a readout to verify whether activation of the TLR2→PMN→B2R axis (where PMN is polymorphonuclear neutrophil) at early stages of mucosal infection had impact on adaptive immunity. Analyzes of T cell recall responses indicated that gingipain drives B2R-dependent generation of IFN-γ-producing Fim T cells in submandibular draining lymph nodes of BALB/c and C57BL/6 mice, whereas IL-17-producing Fim T cells were generated only in BALB/c mice. In summary, our studies suggest that two virulence factors, LPS (an atypical TLR2 ligand) and gingipain, forge a trans-cellular cross-talk between TLR2 and B2R, thus forming an innate axis that guides the development of Fim-specific T cells in mice challenged intrabuccally by P. gingivalis. Ongoing research may clarify whether kinin-driven modulation of T cell responses may also influence the severity of chronic periodontitis.