Francisella inhibits STAT1-mediated signaling in macrophages and prevents activation of antigen-specific T cells.


:Signal transducer and activator of transcription-1 (STAT1) signaling mediate most biological functions of IFNalpha, IFNbeta and IFNgamma although recent studies indicate that IFNgamma can alter expression of several genes via a STAT1-independent pathway. STAT1 is critical for immunity against a variety of intracellular pathogens and some studies show that pathogens evade host immunity by interfering with STAT1 signaling. Here, we have investigated the role of STAT1 in host defense against pulmonary Francisella novicida infection using STAT1-/- mice. In addition, we examined the effect of F. novicida on STAT1 signaling in macrophages and on their ability to activate antigen-specific T cells. Both wild-type (WT) and STAT1-/- BALB/c mice were susceptible to aerosol challenge with 10(3) F. novicida and displayed 100% mortality. However, STAT1-/- mice developed more severe pneumonia, liver pathology and succumbed to infection faster than WT mice. The lungs, liver and hearts from F. novicida-infected STAT1-/- mice also contained more bacteria than WT mice at the time of death. In vitro studies showed that F. novicida suppressed IFNgammaRalpha (alpha subunit of IFNgamma receptor) and MHC class II expression, down-regulated IFNgamma-induced STAT1 activation and reduced nuclear binding of STAT1 in RAW264.7 macrophages. Furthermore, F. novicida-infected BMDM loaded with ovalbumin (OVA) were less efficient in activating OVA-specific CD4+ T cells in vitro. These findings demonstrate that STAT1-mediated signaling participates in the host defense against pulmonary F. novicida infection but it is not sufficient to prevent mortality associated with this infection. Moreover, our results show that F. novicida attenuates STAT1-mediated IFNgamma signaling in macrophages and impairs their ability to activate antigen-specific CD4+ T cells.


Int Immunol


International immunology


Roth KM,Gunn JS,Lafuse W,Satoskar AR




Has Abstract


2009-01-01 00:00:00














  • Class I-restricted cytotoxic T cell recognition of split peptide ligands.

    abstract::We developed a novel approach to probe the molecular basis of TCR recognition of the MHC class I-peptide complex and to determine how constraints placed on peptide binding by the class I molecule influence T cell recognition. We synthesized peptide pairs derived from the N- and C-terminal regions of class I peptide li...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Gillanders WE,Hanson HL,Rubocki RJ,Hansen TH,Connolly JM

    更新日期:1997-01-01 00:00:00

  • TCR-mediated activation promotes GITR upregulation in T cells and resistance to glucocorticoid-induced death.

    abstract::T lymphocytes (pivotal in many inflammatory pathologies) are targets for glucocorticoid hormone (GC). How TCR-mediated activation and GC signaling via glucocorticoid receptor (GR) impact on T-cell fates is not fully defined. We delineated here the expression of a recently identified glucocorticoid-induced TNF receptor...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Zhan Y,Funda DP,Every AL,Fundova P,Purton JF,Liddicoat DR,Cole TJ,Godfrey DI,Brady JL,Mannering SI,Harrison LC,Lew AM

    更新日期:2004-09-01 00:00:00

  • A three-dimensional model of the Fas/APO-1 molecule: cross-reactivity of anti-Fas antibodies explained by structural mimicry of antigenic sites.

    abstract::Fas/APO-1 is a member of the tumor necrosis factor (TNF)/nerve growth factor receptor family. This cell surface protein, when associated with the Fas/APO-1 ligand or specific mAb, elicits an apoptotic response in susceptible cells via an oligomerization of its intracellular domains, termed the'death domains'. We have ...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Fadeel B,Lindberg J,Achour A,Chiodi F

    更新日期:1998-02-01 00:00:00

  • Self-reactive T cells are present in the peripheral lymphoid tissues of cyclosporin A-treated mice.

    abstract::Cyclosporin A (CsA) prevents most immature thymocytes from progressing to a mature phenotype and blocks the deletion of T cells that express self-specific TCR in the small population of cells that achieve maturity. The latter effect may explain the paradoxical observation that this immunosuppressive drug can induce au...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Urdahl KB,Pardoll DM,Jenkins MK

    更新日期:1992-12-01 00:00:00

  • Ubiquitin-like polypeptide inhibits the IgE response of lipopolysaccharide-activated B cells.

    abstract::Monoclonal non-specific suppressor factor (MNSF), a lymphokine produced by a murine hybridoma, was originally found to inhibit the generation of lipopolysaccharide (LPS)-induced Ig-secreting cells. Most recently, we demonstrated the recombinant form of the ubiquitin-like segment (rUbi-L) or MNSF beta, an isoform of MN...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Nakamura M,Nagata T,Xavier M,Tanigawa Y

    更新日期:1996-11-01 00:00:00

  • The response of human B cells to Mycobacterium leprae. Identification of target antigens following polyclonal activation in vitro.

    abstract::We have investigated the B cell response to Mycobacterium leprae in leprosy patients and healthy controls. A comparison of Western-blotted proteins separated by two-dimensional gel electrophoresis and probed with pooled sera from LL and BT patients revealed distinct antigen recognition patterns for the two classificat...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Mahon AC,Gebre N,Nurlign A

    更新日期:1990-01-01 00:00:00

  • Cloning and sequence analysis of a novel beta 2-related integrin transcript from T lymphocytes: homology of integrin cysteine-rich repeats to domain III of laminin B chains.

    abstract::The integrins have been grouped into three subfamilies based on the utilization of three distinct beta chain subunits, beta 1, beta 2, and beta 3. The recent discovery of beta 4 and beta 5 subunits, and the sharing of alpha subunits between beta subfamilies reflects a greater structural and functional diversity of the...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Yuan QA,Jiang WM,Krissansen GW,Watson JD

    更新日期:1990-01-01 00:00:00

  • Inhibition of experimental autoimmune encephalomyelitis in Lewis rats by nasal administration of encephalitogenic MBP peptides: synergistic effects of MBP 68-86 and 87-99.

    abstract::Induction of mucosal tolerance by inhalation of soluble peptides with defined T cell epitopes is receiving much attention as a means of specifically down-regulating pathogenic T cell reactivities in autoimmune and allergic disorders. Experimental autoimmune encephalomyelitis (EAE) induced in the Lewis rat by immunizat...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Liu JQ,Bai XF,Shi FD,Xiao BG,Li HL,Levi M,Mustafa M,Wahren B,Link H

    更新日期:1998-08-01 00:00:00

  • Anti-Semaphorin 3A neutralization monoclonal antibody prevents sepsis development in lipopolysaccharide-treated mice.

    abstract::Semaphorin 3A (Sema3A), originally identified as a potent growth cone collapsing factor in developing sensory neurons, is now recognized as a key player in immune, cardiovascular, bone metabolism and neurological systems. Here we established an anti-Sema3A monoclonal antibody that neutralizes the effects of Sema3A bot...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Yamashita N,Jitsuki-Takahashi A,Ogawara M,Ohkubo W,Araki T,Hotta C,Tamura T,Hashimoto S,Yabuki T,Tsuji T,Sasakura Y,Okumura H,Takaiwa A,Koyama C,Murakami K,Goshima Y

    更新日期:2015-09-01 00:00:00

  • A novel lipid raft-associated glycoprotein, TEC-21, activates rat basophilic leukemia cells independently of the type 1 Fc epsilon receptor.

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    journal_title:International immunology

    pub_type: 杂志文章


    authors: Hálová I,Dráberová L,Dráber P

    更新日期:2002-02-01 00:00:00

  • Involvement of 4F2 antigen expressed on the MHC-negative target cells in the recognition of murine CD3+CD4-CD8- alpha beta (V alpha 4/V beta 2) T cells.

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    journal_title:International immunology

    pub_type: 杂志文章


    authors: Kubota H,Sato M,Ogawa Y,Iwai K,Hattori M,Yoshida T,Minato N

    更新日期:1994-09-01 00:00:00

  • Antibody therapy for the management of severe asthma with eosinophilic inflammation.

    abstract::One of the characteristic features of asthma is chronic airway inflammation typically with eosinophil infiltration. Most asthmatics can be treated successfully with conventional treatment appropriate for their severity, but in some severe cases, asthma cannot be well controlled even with thorough treatment and this co...

    journal_title:International immunology

    pub_type: 杂志文章,评审


    authors: Ohta K,Nagase H,Suzukawa M,Ohta S

    更新日期:2017-07-01 00:00:00

  • Functional consequences of the binding of MHC class II-derived peptides to MHC class II.

    abstract::Three MHC class II-derived synthetic peptides (I-A beta (g7)1-16, I-A beta (g7)52-77 and I-A alpha (g7)63-82YC) were analyzed for their ability to bind to syngeneic and allogeneic MHC class II molecules using a whole cell, competitive peptide binding assay. These studies demonstrated that the A beta (g7)1-16 peptide w...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Feili-Hariri M,Kao H,Mietzner TA,Morel PA

    更新日期:1996-12-01 00:00:00

  • CD28 co-stimulatory signals induce IL-2 receptor expression on antigen-stimulated virgin T cells by an IL-2-independent mechanism.

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    journal_title:International immunology

    pub_type: 杂志文章


    authors: Toyooka K,Maruo S,Iwahori T,Yamamoto N,Tai XG,Abe R,Takahama Y,Murakami M,Uede T,Hamaoka T,Fujiwara H

    更新日期:1996-02-01 00:00:00

  • CCR6hiCD11c(int) B cells promote M-cell differentiation in Peyer's patch.

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    journal_title:International immunology

    pub_type: 杂志文章


    authors: Ebisawa M,Hase K,Takahashi D,Kitamura H,Knoop KA,Williams IR,Ohno H

    更新日期:2011-04-01 00:00:00

  • Multiple nuclear factors bind to novel positive and negative regulatory elements upstream of the human MHC class I gene HLA-A11.

    abstract::Quantitative expression of class I genes varies widely in different tissues, during development and in some neoplastic cells. Regulatory DNA sequences controlling levels of transcription of class I genes have been characterized in the murine and swine promoters. Although some regulatory features appear to be retained ...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Blanchet O,Gazin C,L'Haridon M,Tatari Z,Degos L,Sigaux F,Paul P

    更新日期:1994-10-01 00:00:00

  • Development of dermatitis in CD18-deficient PL/J mice is not dependent on bacterial flora, and requires both CD4+ and CD8+ T lymphocytes.

    abstract::CD18-deficient PL/J mice develop dermatitis characterized by hyperkeratosis, and a mixed dermal and epidermal inflammatory infiltrate. The development of this disease requires low-level CD18 expression and at least two PL/J loci. Currently, the mechanisms by which decreased beta(2) integrin expression on leukocytes pr...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Barlow SC,Xu H,Weaver CT,Lindsey JR,Schoeb TR,Bullard DC

    更新日期:2004-02-01 00:00:00

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    journal_title:International immunology

    pub_type: 杂志文章


    authors: Kamio M,Uchiyama T,Arima N,Itoh K,Ishikawa T,Hori T,Uchino H

    更新日期:1990-01-01 00:00:00

  • Development of Th1 and not Th2 immune responses in mice lacking IFN-regulatory factor-4.

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    journal_title:International immunology

    pub_type: 杂志文章


    authors: Tominaga N,Ohkusu-Tsukada K,Udono H,Abe R,Matsuyama T,Yui K

    更新日期:2003-01-01 00:00:00

  • Anti-B7-1/B7-2 antibody elicits innate-effector responses in macrophages through NF-kappaB-dependent pathway.

    abstract::Blocking T cell co-stimulatory signals by anti-B7-1/B7-2 mAb is an attractive approach to treat autoimmune diseases. However, anti-B7-1/B7-2 mAb treatment is known to exacerbate autoimmune diseases through mechanisms not fully understood. Tumor necrosis factor alpha (TNF-alpha) and reactive oxygen species (ROS) also p...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Khan N,Ghousunnissa S,Jegadeeswaran SM,Thiagarajan D,Hasnain SE,Mukhopadhyay S

    更新日期:2007-04-01 00:00:00

  • Dominant and cryptic antigens in the MHC class I restricted T cell response across a complex minor histocompatibility barrier: analysis and mapping by elution of cellular peptides.

    abstract::T cell responses against complex antigens are often directed against a limited set of immunodominant determinants. We have studied this phenomenon at the level of cellularly processed peptides recognized by CTL in the B6 anti-BALB.B minor histocompatibility (H) barrier, comprising at least 29 antigen loci. B6 anti-BAL...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Wolpert E,Franksson L,Kärre K

    更新日期:1995-06-01 00:00:00

  • Intestinal epithelial cell-derived IL-15 determines local maintenance and maturation of intra-epithelial lymphocytes in the intestine.

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    journal_title:International immunology

    pub_type: 杂志文章


    authors: Zhu Y,Cui G,Miyauchi E,Nakanishi Y,Mukohira H,Shimba A,Abe S,Tani-Ichi S,Hara T,Nakase H,Chiba T,Sehara-Fujisawa A,Seno H,Ohno H,Ikuta K

    更新日期:2020-05-08 00:00:00

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    journal_title:International immunology

    pub_type: 杂志文章


    authors: Han SS,Chung ST,Robertson DA,Chelvarajan RL,Bondada S

    更新日期:1999-06-01 00:00:00

  • LPS-binding protein-deficient mice have an impaired defense against Gram-negative but not Gram-positive pneumonia.

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    journal_title:International immunology

    pub_type: 杂志文章


    authors: Branger J,Florquin S,Knapp S,Leemans JC,Pater JM,Speelman P,Golenbock DT,van der Poll T

    更新日期:2004-11-01 00:00:00

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    journal_title:International immunology

    pub_type: 杂志文章


    authors: Doi T,Obayashi K,Kadowaki T,Fujii H,Koyasu S

    更新日期:2008-04-01 00:00:00

  • Influence of HLA-DR2, HLA-DPw4, and T cell receptor alpha chain genes on the susceptibility to multiple sclerosis.

    abstract::In view of our recent report that T cell receptor (TCR) alpha chain restriction fragment length polymorphism (RFLP) is associated with multiple sclerosis (MS), we have assessed the possibility that HLA-DR2, HLA-DPw4, and TCR alpha chain RFLPs may interact to increase the risk of developing MS. Detection of TCR alpha c...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Sherritt MA,Oksenberg J,de Rosbo NK,Bernard CC

    更新日期:1992-02-01 00:00:00

  • Isoforms of the class II transactivator protein.

    abstract::The class II transactivator (CIITA) controls both the constitutive and IFN-gamma inducible expression of HLA-D genes. In addition, through the squelching of another transactivator CREB-binding protein, CIITA was more recently shown to have a wider cellular function, including cell cycle control or cellular response to...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Barbieri G,Deffrennes V,Prod'homme T,Vedrenne J,Baton F,Cortes C,Fischer A,Bono MR,Lisowska-Grospierre B,Charron D,Alcaïde-Loridan C

    更新日期:2002-08-01 00:00:00

  • Two intermediate-avidity cytotoxic T lymphocyte clones with a disparity between functional avidity and MHC tetramer staining.

    abstract::The efficacy of cytotoxic T lymphocytes (CTL) has been shown to be highly dependent upon their functional avidity (the sensitivity of their cellular response to MHC-peptide complexes). To examine this relationship, we employed target cell lysis as a quantitative measure and established a set of four CTL clones that ex...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Derby MA,Wang J,Margulies DH,Berzofsky JA

    更新日期:2001-06-01 00:00:00

  • Asthmatic changes in mice lacking T-bet are mediated by IL-13.

    abstract::Mice with a targeted deletion of the T-bet gene exhibit spontaneous airway hyperresponsiveness (AHR), airway inflammation, enhanced recovery of T(h)2 cytokines from bronchoalveolar lavage fluid, sub-epithelial collagen deposition and myofibroblast transformation. Here we analyze the mechanisms responsible for the chro...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Finotto S,Hausding M,Doganci A,Maxeiner JH,Lehr HA,Luft C,Galle PR,Glimcher LH

    更新日期:2005-08-01 00:00:00

  • Prostanoids and leukotrienes in the pathophysiology of atopic dermatitis and psoriasis.

    abstract::Lipid mediators, such as prostanoids and leukotrienes (LTs), exert a range of actions through their own receptors on cell surfaces in various pathophysiological conditions. It has been reported that the production of prostanoids and LTs is significantly elevated in the skin lesions of some chronic inflammatory skin di...

    journal_title:International immunology

    pub_type: 杂志文章,评审


    authors: Honda T,Kabashima K

    更新日期:2019-08-23 00:00:00