Effective clearance of intracellular Leishmania major in vivo requires Pten in macrophages.

Abstract:

:Leishmaniases are a major international public health problem, and macrophages are crucial for host resistance to this parasite. To determine if phosphatase and tensin homologue deleted on chromosome ten (Pten), a negative regulator of the PI3K pathway, plays a role in macrophage-mediated resistance to Leishmania, we generated C57BL/6 mice lacking Pten specifically in macrophages (LysMCrePten(flox/flox) mice). Examination of lesions resulting from Leishmania major infection showed that LysMCrePten(flox/flox) mice were more susceptible to the parasite than wild-type (WT) mice in the early phase of the infection, but were eventually able to eliminate the pathogen. In vitro Pten-deficient macrophages showed a reduced ability to kill parasites in response to IFN-gamma treatment, possibly because the mutant cells exhibited decreased TNF secretion that correlated with reductions in inducible nitric oxide synthase expression and nitric oxide production. In response to various TLR ligands, Pten-deficient macrophages produced less TNF and IL-12 but more IL-10 than WT cells. However, analysis of cells in the lymph nodes draining L. major inoculation sites indicated that both LysMCrePten(flox/flox) and WT mice developed normal Th1 responses following L. major infection, in line with the ability of LysMCrePten(flox/flox) mice to eventually eliminate the parasite. Our results indicate that the efficient clearance of intracellular parasites requires Pten in macrophages.

journal_name

Eur J Immunol

authors

Kuroda S,Nishio M,Sasaki T,Horie Y,Kawahara K,Sasaki M,Natsui M,Matozaki T,Tezuka H,Ohteki T,Förster I,Mak TW,Nakano T,Suzuki A

doi

10.1002/eji.200737302

subject

Has Abstract

pub_date

2008-05-01 00:00:00

pages

1331-40

issue

5

eissn

0014-2980

issn

1521-4141

journal_volume

38

pub_type

杂志文章
  • Persisting alloantigen prevents primed CD45RC- CD4 T cells from inducing allograft rejection: implications for immunological memory.

    abstract::Antigen stimulation induces specific CD4 T cells to change from a resting phenotype (CD45RC+) to a "memory" phenotype (CD45RC-), an isoform switch that is reversible and regulated by persisting antigen. We show here that CD4 T cells responsible for mediating allograft rejection undergo a similar CD45RC+ to CD45RC- swi...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1521-4141(199907)29:07<2177::AID-IMM

    authors: Yang CP,Bell EB

    更新日期:1999-07-01 00:00:00

  • Granzyme A expression by normal rat natural killer (NK) cells in vivo and by interleukin 2-activated NK cells in vitro.

    abstract::Granzyme A (TSP-1) is a serine esterase expressed in cytotoxic T and natural killer (NK) cell lines. Its presence in in vivo primed T cells is disputed at present. Here we show that normal rat NK cells contain granzyme A in vivo and that its expression is augmented by their short-term in vitro treatment with IL 2. Gra...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830190328

    authors: Velotti F,Palmieri G,Morrone S,Piccoli M,Frati L,Santoni A

    更新日期:1989-03-01 00:00:00

  • The TNF receptor family member CD27 signals to Jun N-terminal kinase via Traf-2.

    abstract::CD27 is a lymphocyte-specific member of the TNF receptor (TNFR) family. It is a costimulatory molecule for peripheral T cells, as defined by its ability to enhance the TCR-induced proliferative response. We show here that CD27 augments TCR-induced Jun N-terminal kinase (JNK) activity in primary murine lymph node T cel...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1521-4141(199807)28:07<2208::AID-IMM

    authors: Gravestein LA,Amsen D,Boes M,Calvo CR,Kruisbeek AM,Borst J

    更新日期:1998-07-01 00:00:00

  • Evidence for Th2 cell-mediated suppression of antibody responses in transgenic, beef insulin-tolerant mice.

    abstract::Clonal deletion, anergy and suppression have all been considered mechanisms of immunological tolerance. Although adoptive transfer of immunosuppression has been shown to occur in the periphery, particularly for transplantation tolerance, it has proven difficult to characterize this phenomenon further, due to the lack ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830250917

    authors: Teng YT,Gorczynski RM,Iwasaki S,Williams DB,Hozumi N

    更新日期:1995-09-01 00:00:00

  • CD11c provides an effective immunotarget for the generation of both CD4 and CD8 T cell responses.

    abstract::The magnitude and quality of T cell responses generated when Ag is targeted to receptors on DC is influenced by both the specific receptor targeted and its distribution among DC subsets. Here we examine the targeting of the model Ag OVA to potential DC targets, including CD11c, CD205, MHC class II, CD40, TLR2 and Fcga...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200838302

    authors: Castro FV,Tutt AL,White AL,Teeling JL,James S,French RR,Glennie MJ

    更新日期:2008-08-01 00:00:00

  • Urtica dioica agglutinin, a V beta 8.3-specific superantigen, prevents the development of the systemic lupus erythematosus-like pathology of MRL lpr/lpr mice.

    abstract::The V beta 8.3-specific superantigenic lectin Urtica dioica agglutinin (UDA) was used to delete the V beta 8.3+ T cells in MRL lpr/lpr mice. In contrast to the systemic lupus erythematosus-like pathology which progresses with age in the phosphate-buffered saline-injected MRL lpr/lpr controls, UDA-treated animals did n...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830260807

    authors: Musette P,Galelli A,Chabre H,Callard P,Peumans W,Truffa-Bachi P,Kourilsky P,Gachelin G

    更新日期:1996-08-01 00:00:00

  • The mechanism of synergistic complement-mediated lysis of rat red cells by monoclonal IgG antibodies.

    abstract::The mechanism of synergistic complement-mediated lysis of rat red cells was investigated using rat monoclonal antibodies against class I RT1Aa antigens. The increased lytic activity when using two antibodies simultaneously is due to the increase in the number of activated C1 molecules on the cell surface and this resu...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830130806

    authors: Hughes-Jones NC,Gorick BD,Howard JC

    更新日期:1983-08-01 00:00:00

  • Chemotactic activity on mononuclear cells in the cerebrospinal fluid of patients with viral meningitis is mediated by interferon-gamma inducible protein-10 and monocyte chemotactic protein-1.

    abstract::In viral meningitis the inflammatory response involves activated T cells and monocytes which are recruited into the subarachnoid space. To identify the chemotactic signals attracting the cells to the site of infection in the meninges, we measured the levels of two CXC chemokines, interferon-gamma (IFN-gamma) inducible...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830271004

    authors: Lahrtz F,Piali L,Nadal D,Pfister HW,Spanaus KS,Baggiolini M,Fontana A

    更新日期:1997-10-01 00:00:00

  • Effect of cloned interferon-gamma on expression of H-2 and Ia antigens on cell lines of hemopoietic, lymphoid, epithelial, fibroblastic and neuronal origin.

    abstract::Interferon-gamma (IFN-gamma), tested in the form of the product of a cloned murine IFN-gamma gene, was found to increase the expression of H-2 antigens on cultured cell lines of a wide variety of cell types including factor-dependent hemopoietic cells, pre-B and B cells, macrophages, T cells, mast cells and cell lines...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830140110

    authors: Wong GH,Clark-Lewis I,Harris AW,Schrader JW

    更新日期:1984-01-01 00:00:00

  • MHC class II-independent CD25+ CD4+ CD8alpha beta+ alpha beta T cells attenuate CD4+ T cell-induced transfer colitis.

    abstract::CD4+ alpha beta T cell populations that develop in mice deficient in MHC class II (through 'knockout' of either the Aalpha, or the Abeta chain of the I-A(b) molecule) comprise a major 'single-positive' (SP) CD4+ CD8- subset (60-90%) and a minor 'double-positive' (DP) CD4+ CD8alpha beta+ subset (10-40%). Many DP T cell...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200324463

    authors: Krajina T,Leithäuser F,Reimann J

    更新日期:2004-03-01 00:00:00

  • New insights into cathelicidin modulation of adaptive immunity.

    abstract::Cathelicidins are a family of host defence peptides that are known to selectively alter innate immunity in response to infection and other changes in immune status. A study in this issue of the European Journal of Immunology elucidates a new role for mouse cathelin-related antimicrobial peptide in the adaptive immune ...

    journal_title:European journal of immunology

    pub_type: 评论,杂志文章

    doi:10.1002/eji.201142055

    authors: Wuerth K,Hancock RE

    更新日期:2011-10-01 00:00:00

  • T cell responses are governed by avidity and co-stimulatory thresholds.

    abstract::We analyzed the avidity and CD28-mediated co-stimulatory requirements for the activation of T cells in vivo and in vitro. The strength of the T cell/antigen-presenting cell interaction was varied by using altered peptide ligands for stimulation. Co-stimulatory requirements were studied using T cells from CD28-deficien...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830260908

    authors: Bachmann MF,Sebzda E,Kündig TM,Shahinian A,Speiser DE,Mak TW,Ohashi PS

    更新日期:1996-09-01 00:00:00

  • Transendothelial chemotaxis of human alpha/beta and gamma/delta T lymphocytes to chemokines.

    abstract::Two subpopulations of human T lymphocytes expressing different antigen receptors, alpha/beta and gamma/delta, emigrate into inflamed tissues in distinctive patterns. We compared the transmigration of alpha/beta and gamma/delta T cells to C-C and C-X-C chemokines using an in vitro transendothelial chemotaxis assay. The...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1521-4141(199801)28:01<104::AID-IMMU

    authors: Roth SJ,Diacovo TG,Brenner MB,Rosat JP,Buccola J,Morita CT,Springer TA

    更新日期:1998-01-01 00:00:00

  • Correlation between the occurrence of lupus nephritis, anti-erythrocyte autoantibodies and V kappa haplotype in NZB x 129/J and NZB x SM/J recombinant inbred murine strains.

    abstract::The NZB mouse is genetically predisposed to the development of autoimmune disease that resembles the human autoimmune systemic lupus erythematosus and autoimmune hemolytic anemia, with increased titers of anti-DNA, and Coombs' autoantibodies. The various autoimmune traits are controlled separately by a limited number ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830210415

    authors: Bailey NC,Bona A,Dikman S,Bonilla F,Alt FW,Bona C

    更新日期:1991-04-01 00:00:00

  • Identification of a new epitope of the 4F2/44D7 molecular complex present on sarcolemma and isolated cardiac fibers.

    abstract::The murine monoclonal antibody (mAb) CB43, raised against the K-562 erythroleukemia line, reacts with monocytes, tissue macrophages, thymocytes and with all the human lines tested but not with resting lymphocytes, large granular lymphocytes, granulocytes and erythrocytes. However, activated lymphocytes and natural kil...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830190102

    authors: Bellone G,Alloatti G,Levi R,Geuna M,Tetta C,Peruzzi L,Letarte M,Malavasi F

    更新日期:1989-01-01 00:00:00

  • Mycobacterium tuberculosis exploits the CD95/CD95 ligand system of gammadelta T cells to cause apoptosis.

    abstract::Vgamma9/Vdelta2+ T cells specifically recognize Mycobacterium tuberculosis in vitro and are precociously recruited in early mycobacterial lesions. Even if gammadelta T cells are only fortuitously detected in granulomas or bronchoalveolar lavages of patients with active pulmonary tuberculosis, a role in shaping the mat...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1521-4141(199806)28:06<1798::AID-IMM

    authors: Manfredi AA,Heltai S,Rovere P,Sciorati C,Paolucci C,Galati G,Rugarli C,Vaiani R,Clementi E,Ferrarini M

    更新日期:1998-06-01 00:00:00

  • Human leukocyte function-associated antigens on lympho-hemopoietic precursor cells.

    abstract::The expression of human leukocyte function-associated antigens (HLFA, equivalents of murine LFA-1) was studied on early lympho-hemopoietic cells in infant thymus and normal bone marrow by double immunofluorescence methods, cell sorting and colony-forming assays. Monoclonal antibodies MHM-24 recognizing the alpha chain...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830160513

    authors: Campana D,Sheridan B,Tidman N,Hoffbrand AV,Janossy G

    更新日期:1986-05-01 00:00:00

  • Studies on the relationships between the immunogenicity and catabolism of antigens and their binding to the surface of macrophages.

    abstract::The relationship between immunogenicity of Shigella paradysenteriae, the branched synthetic polypeptide poly-L (Tyr, Glu)-polylpro-polyllys [(T, G)-Pro--L] and human albumin (HSA) interacting with macrophages and kinetics of antigen degradation and degree of binding to the cell surface was studied. Following thioglyco...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830061107

    authors: Gallily R,Bar-Eli M

    更新日期:1976-11-01 00:00:00

  • The TGF-beta response to Leishmania chagasi in the absence of IL-12.

    abstract::Cure of leishmaniasis requires a type 1 immune response characterized by IFN-gamma production. Leishmania major infection leads to a type 2 response suppressing cure of susceptible BALB/c mice, and L. major causes an exacerbated type 2 response in mouse strains with a gene knockout (KO) such that they lack IL-12p40 (I...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/1521-4141(200212)32:12<3556::AID-IMMU3556>

    authors: Wilson ME,Recker TJ,Rodriguez NE,Young BM,Burnell KK,Streit JA,Kline JN

    更新日期:2002-12-01 00:00:00

  • The nature of active and passive thyroglobulin binding lymphoid cells in Obese strain (OS) chickens.

    abstract::Thyroglobulin-binding lymphoid cells were identified in the spleen of Obese strain (DS) chickens by their capacity to form rosettes with thyroglobulin-coated chicken red blood cells. The nature of these cells was studied in inhibition experiments using turkey anti-chicken bursa or thymus cell sera and rabbit antisera ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830050810

    authors: Richter E,Wick G,Schauenstein K

    更新日期:1975-08-01 00:00:00

  • In vivo control of endosomal architecture by class II-associated invariant chain and cathepsin S.

    abstract::The invariant chain (Ii) is a chaperone that regulates assembly and transport of class II MHC molecules. In the absence of the lysosomal protease cathepsin S (CatS), degradation of Ii is impaired and an Ii remnant that extends from the N terminus to about residue 110 accumulates in class II MHC-positive endosomal comp...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200526323

    authors: Boes M,van der Wel N,Peperzak V,Kim YM,Peters PJ,Ploegh H

    更新日期:2005-09-01 00:00:00

  • Activated T cells enhance nitric oxide production by murine splenic macrophages through gp39 and LFA-1.

    abstract::Macrophages can be stimulated to produce a relatively large amount of nitric oxide, which is an important component in macrophage-mediated defense mechanisms and regulation of T cell activities. It has been known that T helper (Th) cell activation requires intimate physical interaction between T helper cells and macro...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830250152

    authors: Tian L,Noelle RJ,Lawrence DA

    更新日期:1995-01-01 00:00:00

  • The serine phosphatases PP1 and PP2A associate with and activate the actin-binding protein cofilin in human T lymphocytes.

    abstract::Cofilin, an actin-depolymerizing protein, is essential for the functional dynamics of the actin cytoskeleton and for cell viability. In unstimulated human peripheral blood T lymphocytes cofilin is phosphorylated and localized in the cytoplasm. Following co-stimulation through accessory receptors (e.g. CD2 or CD28) - h...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/1521-4141(2000012)30:12<3422::AID-IMMU3422

    authors: Ambach A,Saunus J,Konstandin M,Wesselborg S,Meuer SC,Samstag Y

    更新日期:2000-12-01 00:00:00

  • Cellular requirements for anti-DNA production induced in mice by immunization with bacterial DNA.

    abstract::To further define DNA immunization as a model for anti-DNA production, we investigated the cellular requirements for this response in mice immunized with single-stranded DNA from E. coli. The anti-DNA responses of genetically immune-deficient mice and congenic controls were measured by ELISA after immunization with E....

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830200825

    authors: Gilkeson GS,Pritchard AJ,Pisetsky DS

    更新日期:1990-08-01 00:00:00

  • Systemic immune responses induced by mucosal administration of lipopeptides without adjuvant.

    abstract::We recently reported that parenteral injection of malaria palmitoyl-tailed peptides without adjuvant efficiently induces B, Th and CTL responses. We now show that intranasal (IN) or sub-lingual (SL) delivery of such lipopeptides induces strong systemic immune responses, as demonstrated by specific Th cell responses fr...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/1521-4141(200208)32:8<2274::AID-IMMU2274>3

    authors: BenMohamed L,Belkaid Y,Loing E,Brahimi K,Gras-Masse H,Druilhe P

    更新日期:2002-08-01 00:00:00

  • Functional CD1a is stabilized by exogenous lipids.

    abstract::Self-glycosphingolipids bind to surface CD1 molecules and are readily displaced by other CD1 ligands. This capacity to exchange antigens at the cell surface is not common to other antigen-presenting molecules and its physiological importance is unclear. Here we show that a large pool of cell-surface CD1a, but not CD1b...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200535544

    authors: Manolova V,Kistowska M,Paoletti S,Baltariu GM,Bausinger H,Hanau D,Mori L,De Libero G

    更新日期:2006-05-01 00:00:00

  • Towards an idiotype vaccine against mammary tumors. Induction of an immune response to breast cancer-associated antigens by anti-idiotypic antibodies.

    abstract::Previously we have reported on the production of two sets of human monoclonal antibodies reacting with mouse mammary tumor virus (MMTV) and human mammary tumor virus (HuMTV) cross-reacting antigens. B11 is a monoclonal IgG generated by the human-human hybridoma technique using axillary lymph node of breast cancer pati...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830181109

    authors: Smorodinsky NI,Ghendler Y,Bakimer R,Chaitchuk S,Keydar I,Shoenfeld Y

    更新日期:1988-11-01 00:00:00

  • Dendritic cells erase bad memory.

    abstract::DC not only activate CD4 T (Th) cell and cytotoxic CD8 T cell (CTL) responses against pathogens, but they also tolerize autoreactive T cells in order to avoid autoimmunity. Previous studies have demonstrated that steady-state DC can tolerize naïve CTL, naïve Th cells and memory CTL. A study in this issue of the Europe...

    journal_title:European journal of immunology

    pub_type:

    doi:10.1002/eji.201040704

    authors: Kurts C

    更新日期:2010-07-01 00:00:00

  • Serological analysis of antigen-specific helper factors specific for poly-L(Tyr, Glu)-poly-DLAla--poly-LLys [(T, G)-A--L] and L Glu60-LAla30-LTyr10 (GAT).

    abstract::In vitro prepared antigen-specific helper factors reactive to the synthetic polypeptide antigens poly-L(Tyr, Glu)-poly-DLAla--poly-LLys [(T, G)-A--L] or LGlu60-LAla30-LTyr10 (GAT) and bearing Ia determinants were analyzed serologically to determine the nature of the Ia determinants they expressed. I subregion-specific...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830090703

    authors: Howie S,Parish CR,David CS,McKenzie IF,Maurer PH,Feldmann M

    更新日期:1979-07-01 00:00:00

  • Activation of the alternative pathway of complement: efficient fluid-phase amplification by blockade of the regulatory complement protein beta1H through sulfated polyanions.

    abstract::Current concepts of activation of the alternative pathway of complement (APC) focus on the central role of an amplification mechanism triggered by C3b which is covalently bound to the surfact of activating substances. Using sulfated polyanions as model substances, an efficient fluid-phase activation of complement is d...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830110405

    authors: Bitter-Suermann D,Burger R,Hadding U

    更新日期:1981-04-01 00:00:00