Mesenchymal stromal (stem) cells suppress pro-inflammatory cytokine production but fail to improve survival in experimental staphylococcal toxic shock syndrome.

Abstract:

BACKGROUND:Toxic shock syndrome (TSS) is caused by an overwhelming host-mediated response to bacterial superantigens produced mainly by Staphylococcus aureus and Streptococcus pyogenes. TSS is characterized by aberrant activation of T cells and excessive release of pro-inflammatory cytokines ultimately resulting in capillary leak, septic shock, multiple organ dysfunction and high mortality rates. No therapeutic or vaccine has been approved by the U.S. Food and Drug Administration for TSS, and novel therapeutic strategies to improve clinical outcome are needed. Mesenchymal stromal (stem) cells (MSCs) are stromal cells capable of self-renewal and differentiation. Moreover, MSCs have immunomodulatory properties, including profound effects on activities of T cells and macrophages in specific contexts. Based on the critical role of host-derived immune mediators in TSS, we hypothesized that MSCs could modulate the host-derived proinflammatory response triggered by Staphylococcal enterotoxin B (SEB) and improve survival in experimental TSS. METHODS:Effects of MSCs on proinflammatory cytokines in peripheral blood were measured in wild-type C57BL/6 mice injected with 50 μg of SEB. Effects of MSCs on survival were monitored in fatal experimental TSS induced by consecutive doses of D-galactosamine (10 mg) and SEB (10 μg) in HLA-DR4 transgenic mice. RESULTS:Despite significantly decreasing serum levels of IL-2, IL-6 and TNF induced by SEB in wild-type mice, human MSCs failed to improve survival in experimental TSS in HLA-DR4 transgenic mice. Similarly, a previously described downstream mediator of human MSCs, TNF-stimulated gene 6 (TSG-6), did not significantly improve survival in experimental TSS. Furthermore, murine MSCs, whether unstimulated or pre-treated with IFNγ, failed to improve survival in experimental TSS. CONCLUSIONS:Our results suggest that the immunomodulatory effects of MSCs are insufficient to rescue mice from experimental TSS, and that mediators other than IL-2, IL-6 and TNF are likely to play critical mechanistic roles in the pathogenesis of experimental TSS.

journal_name

BMC Immunol

journal_title

BMC immunology

authors

Kim H,Darwish I,Monroy MF,Prockop DJ,Liles WC,Kain KC

doi

10.1186/1471-2172-15-1

subject

Has Abstract

pub_date

2014-01-14 00:00:00

pages

1

issn

1471-2172

pii

1471-2172-15-1

journal_volume

15

pub_type

杂志文章
  • The discriminative capacity of soluble Toll-like receptor (sTLR)2 and sTLR4 in inflammatory diseases.

    abstract:BACKGROUND:The extracellular domains of cytokine receptors are released during inflammation, but little is known about the shedding of Toll-like receptors (TLR) and whether they can be used as diagnostic biomarkers. METHODS:The release of sTLR2 and sTLR4 was studied in in-vitro stimulations, as well as in-vivo during ...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/s12865-014-0055-y

    authors: Ten Oever J,Kox M,van de Veerdonk FL,Mothapo KM,Slavcovici A,Jansen TL,Tweehuysen L,Giamarellos-Bourboulis EJ,Schneeberger PM,Wever PC,Stoffels M,Simon A,van der Meer JW,Johnson MD,Kullberg BJ,Pickkers P,Pachot A,Jooste

    更新日期:2014-11-19 00:00:00

  • Combined TLR2 and TLR4 ligation in the context of bacterial or helminth extracts in human monocyte derived dendritic cells: molecular correlates for Th1/Th2 polarization.

    abstract:BACKGROUND:Recognition of pathogens by dendritic cells (DCs) through interaction with pattern recognition receptors, including Toll like receptors (TLR), is crucial for the initiation of appropriate polarized T helper (Th) cell responses. Yet, the characteristics and differences in molecular profiles of DCs with differ...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/1471-2172-10-9

    authors: van Riet E,Everts B,Retra K,Phylipsen M,van Hellemond JJ,Tielens AG,van der Kleij D,Hartgers FC,Yazdanbakhsh M

    更新日期:2009-02-04 00:00:00

  • Efficient adenovirus-mediated gene transfer into primary T cells and thymocytes in a new coxsackie/adenovirus receptor transgenic model.

    abstract:BACKGROUND:Gene transfer studies in primary T cells have suffered from the limitations of conventional viral transduction or transfection techniques. Replication-defective adenoviral vectors are an attractive alternative for gene delivery. However, naive lymphocytes are not readily susceptible to infection with adenovi...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/1471-2172-3-4

    authors: Hurez V,Dzialo-Hatton R,Oliver J,Matthews RJ,Weaver CT

    更新日期:2002-05-02 00:00:00

  • Genomic locus on chromosome 1 regulates susceptibility to spontaneous arthritis in mice deficiency of IL-1RA.

    abstract:BACKGROUND:To understand the role of genetic factors on chromosome 1 in the regulation of spontaneous arthritis in mice deficient in IL-1 receptor antagonist protein (IL_1RA), we previously used speed congenic breeding to transfer the QTL region from DBA/1(-/-) mice that are resistant to spontaneous arthritis into BALB...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/s12865-014-0057-9

    authors: Deng N,Jiao Y,Cao Y,Liu X,Ma Y,Hasty KA,Brand DD,Stuart JM,Gu W

    更新日期:2014-12-09 00:00:00

  • The role of CXCR3 and its ligands expression in Brucellar spondylitis.

    abstract:AIM:Brucellar spondylitis (BS) is one of the most serious complications of brucellosis. CXCR3 is closely related to the severity of disease infection. This research aimed to study the degree of BS inflammatory damage through analyzing the expression levels of CXCR3 and its ligands (CXCL9 and CXCL10) in patients with BS...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/s12865-020-00390-9

    authors: Hu X,Shang X,Wang L,Fan J,Wang Y,Lv J,Nazierhan S,Wang H,Wang J,Ma X

    更新日期:2020-11-18 00:00:00

  • Streptococcus sanguinis-induced cytokine and matrix metalloproteinase-1 release from platelets.

    abstract:BACKGROUND:Streptococcus sanguinis (S.sanguinis), a predominant bacterium in the human oral cavity, has been widely associated with the development of infective endocarditis. Platelets play both a haemostatic function and can influence both innate and adaptive immune responses. Previous studies have shown that S.sangui...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/1471-2172-15-15

    authors: Cognasse F,Hamzeh-Cognasse H,Chabert A,Jackson E,Arthaud CA,Garraud O,McNicol A

    更新日期:2014-04-22 00:00:00

  • The immunoregulatory role of alpha enolase in dendritic cell function during Chlamydia infection.

    abstract:BACKGROUND:We have previously reported that interleukin-10 (IL-10) deficient dendritic cells (DCs) are potent antigen presenting cells that induced elevated protective immunity against Chlamydia. To further investigate the molecular and biochemical mechanism underlying the superior immunostimulatory property of IL-10 d...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/s12865-017-0212-1

    authors: Ryans K,Omosun Y,McKeithen DN,Simoneaux T,Mills CC,Bowen N,Eko FO,Black CM,Igietseme JU,He Q

    更新日期:2017-05-19 00:00:00

  • Differential expression of CD300a/c on human TH1 and TH17 cells.

    abstract:BACKGROUND:Human memory CD4+ T cells can be either CD300a/c+ or CD300a/c- and subsequent analyses showed that CD4+ effector memory T (T(EM)) cells are mostly CD300a/c+, whereas CD4+ central memory T (T(CM)) cells have similar frequencies of CD300a/c+ and CD300a/c- cells. RESULTS:Extensive phenotypical and functional c...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/1471-2172-12-62

    authors: Simhadri VR,Mariano JL,Zhou Q,DeBell KE,Borrego F

    更新日期:2011-11-02 00:00:00

  • Changes in colon gene expression associated with increased colon inflammation in interleukin-10 gene-deficient mice inoculated with Enterococcus species.

    abstract:BACKGROUND:Inappropriate responses to normal intestinal bacteria may be involved in the development of Inflammatory Bowel Diseases (IBD, e.g. Crohn's Disease (CD), Ulcerative Colitis (UC)) and variations in the host genome may mediate this process. IL-10 gene-deficient (Il10-/-) mice develop CD-like colitis mainly in t...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/1471-2172-11-39

    authors: Barnett MP,McNabb WC,Cookson AL,Zhu S,Davy M,Knoch B,Nones K,Hodgkinson AJ,Roy NC

    更新日期:2010-07-15 00:00:00

  • Multi-layered Gag-specific immunodominant responses contribute to improved viral control in the CRF01_AE subtype of HIV-1-infected MSM subjects.

    abstract:BACKGROUND:The purpose of this study was to characterize specific cytotoxic T-cell (CTL) responses in men who have sex with men (MSM) subjects infected with the human immunodeficiency virus type 1 (HIV-1) CRF01_AE subtype during the first year of infection and impacts on viral control and evolution. RESULTS:Fifteen HI...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/s12865-016-0166-8

    authors: Jiang F,Han X,Zhang H,Zhao B,An M,Xu J,Chu Z,Dong T,Shang H

    更新日期:2016-08-30 00:00:00

  • Mycobacterial glycolipids di-O-acylated trehalose and tri-O-acylated trehalose downregulate inducible nitric oxide synthase and nitric oxide production in macrophages.

    abstract:BACKGROUND:Tuberculosis (TB) remains a serious human health problem that affects millions of people in the world. Understanding the biology of Mycobacterium tuberculosis (Mtb) is essential for tackling this devastating disease. Mtb possesses a very complex cell envelope containing a variety of lipid components that par...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/s12865-015-0102-3

    authors: Espinosa-Cueto P,Escalera-Zamudio M,Magallanes-Puebla A,López-Marín LM,Segura-Salinas E,Mancilla R

    更新日期:2015-06-23 00:00:00

  • HLA class I supertypes: a revised and updated classification.

    abstract:BACKGROUND:Class I major histocompatibility complex (MHC) molecules bind, and present to T cells, short peptides derived from intracellular processing of proteins. The peptide repertoire of a specific molecule is to a large extent determined by the molecular structure accommodating so-called main anchor positions of th...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/1471-2172-9-1

    authors: Sidney J,Peters B,Frahm N,Brander C,Sette A

    更新日期:2008-01-22 00:00:00

  • Standardization and performance evaluation of mononuclear cell cytokine secretion assays in a multicenter study.

    abstract:BACKGROUND:Cryopreservation of peripheral blood mononuclear cells has been used to preserve and standardize immunologic measurements for multicenter studies, however, effects of cryopreservation on cytokine responses are incompletely understood. In designing immunologic studies for a new multicenter birth cohort study ...

    journal_title:BMC immunology

    pub_type: 杂志文章,多中心研究

    doi:10.1186/1471-2172-7-29

    authors: Shreffler WG,Visness CM,Burger M,Cruikshank WW,Lederman HM,de la Morena M,Grindle K,Calatroni A,Sampson HA,Gern JE

    更新日期:2006-12-12 00:00:00

  • Secretion of celiac disease autoantibodies after in vitro gliadin challenge is dependent on small-bowel mucosal transglutaminase 2-specific IgA deposits.

    abstract:BACKGROUND:In celiac disease gluten, the disease-inducing toxic component in wheat, induces the secretion of autoantibodies which are targeted against transglutaminase 2 (TG2). These autoantibodies are produced in the small-intestinal mucosa, where they can be found deposited extracellularly below the epithelial baseme...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/1471-2172-9-6

    authors: Stenman SM,Lindfors K,Korponay-Szabo IR,Lohi O,Saavalainen P,Partanen J,Haimila K,Wieser H,Mäki M,Kaukinen K

    更新日期:2008-02-29 00:00:00

  • Differential utilization of NF-kappaB RELA and RELB in response to extracellular versus intracellular polyIC stimulation in HT1080 cells.

    abstract:BACKGROUND:Pattern recognition receptors (PRRs) for double-stranded RNA (dsRNA) are components of innate immunity that recognize the presence of viral infection and initiate efficient defense mechanisms. In addition to previously well-characterized signaling pathways that are mediated by PKR and TLR3, new intracellular...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/1471-2172-12-15

    authors: Yun JJ,Tsao MS,Der SD

    更新日期:2011-02-10 00:00:00

  • Co-inherited mutations of Fas and caspase-10 in development of the autoimmune lymphoproliferative syndrome.

    abstract:BACKGROUND:Autoimmune lymphoproliferative syndrome (ALPS) is a rare inherited disorder characterized by defective function of Fas, autoimmune manifestations that predominantly involve blood cells, polyclonal accumulation of lymphocytes in the spleen and lymph nodes with lymphoadenomegaly and/or splenomegaly, and expans...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/1471-2172-8-28

    authors: Cerutti E,Campagnoli MF,Ferretti M,Garelli E,Crescenzio N,Rosolen A,Chiocchetti A,Lenardo MJ,Ramenghi U,Dianzani U

    更新日期:2007-11-13 00:00:00

  • A selective and potent CXCR3 antagonist SCH 546738 attenuates the development of autoimmune diseases and delays graft rejection.

    abstract:BACKGROUND:The CXCR3 receptor and its three interferon-inducible ligands (CXCL9, CXCL10 and CXCL11) have been implicated as playing a central role in directing a Th1 inflammatory response. Recent studies strongly support that the CXCR3 receptor is a very attractive therapeutic target for treating autoimmune diseases, s...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/1471-2172-13-2

    authors: Jenh CH,Cox MA,Cui L,Reich EP,Sullivan L,Chen SC,Kinsley D,Qian S,Kim SH,Rosenblum S,Kozlowski J,Fine JS,Zavodny PJ,Lundell D

    更新日期:2012-01-10 00:00:00

  • Accumulation of marginal zone B cells and accelerated loss of follicular dendritic cells in NF-kappaB p50-deficient mice.

    abstract:BACKGROUND:Marginal zone (MZ) B cells play important roles in the early phases of humoral immune responses. In addition to possessing an inherent capacity to rapidly differentiate into antibody secreting cells, MZ B cells also help to regulate the fate of both T-independent and T-dependent blood-borne antigens in the s...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/1471-2172-6-8

    authors: Ferguson AR,Corley RB

    更新日期:2005-04-18 00:00:00

  • Pathogen recognition by NK cells amplifies the pro-inflammatory cytokine production of monocyte-derived DC via IFN-γ.

    abstract:BACKGROUND:Besides their prominent role in the elimination of infected or malignantly transformed cells, natural killer (NK) cells serve as modulators of adaptive immune responses. Enhancing bidirectional crosstalk between NK cells and dendritic cells (DC) is considered a promising tool to potentiate cancer vaccines. W...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/s12865-018-0247-y

    authors: Oth T,Habets THPM,Germeraad WTV,Zonneveld MI,Bos GMJ,Vanderlocht J

    更新日期:2018-02-13 00:00:00

  • NK cell predicts the severity of acute graft-versus-host disease in patients after allogeneic stem cell transplantation using antithymocyte globulin (ATG) in pretreatment scheme.

    abstract:BACKGROUND:Graft-versus-host disease (GVHD) is one of the most complex complications after allogeneic stem cell transplantation. Current standard of grading system is based on clinical symptoms in skin, liver and intestinal. However, it's difficult to differ GVHD and its extent just by clinical manifestation. Here we r...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/s12865-019-0326-8

    authors: Zhang P,Yang S,Zou Y,Yan X,Wu H,Zhou M,Sun YC,Zhang Y,Zhu H,Xu K,Wang Y,Sheng LX,Mu Q,Sun L,Ouyang G

    更新日期:2019-12-09 00:00:00

  • Down selecting adjuvanted vaccine formulations: a comparative method for harmonized evaluation.

    abstract:BACKGROUND:The need for rapid and accurate comparison of panels of adjuvanted vaccine formulations and subsequent rational down selection, presents several challenges for modern vaccine development. Here we describe a method which may enable vaccine and adjuvant developers to compare antigen/adjuvant combinations in a ...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/s12865-018-0245-0

    authors: Younis SY,Barnier-Quer C,Heuking S,Sommandas V,Brunner L,Vd Werff N,Dubois P,Friede M,Kocken C,Collin N,Remarque E

    更新日期:2018-01-31 00:00:00

  • Association of proinflammatory genes expression with serum interleukin 1β and free fatty acids in metabolically healthy and unhealthy abdominally obese individuals: a case-control study.

    abstract:BACKGROUND:Proinflammatory genes are highly expressed in several metabolic disorders associated with obesity. But it is not clarified whether gene expression levels and downstream inflammatory markers are related to the metabolic state or the presence of obesity. Hence, the present study aimed to compare Toll-Like Rece...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/s12865-019-0303-2

    authors: Amiri P,Baradaran B,Saghafi-Asl M,Naghizadeh M,Shanehbandi D,Karamzad N,Vahed SZ

    更新日期:2019-07-04 00:00:00

  • The effects of storage temperature on PBMC gene expression.

    abstract:BACKGROUND:Cryopreservation of peripheral blood mononuclear cells (PBMCs) is a common and essential practice in conducting research. There are different reports in the literature as to whether cryopreserved PBMCs need to only be stored ≤ -150 °C or can be stored for a specified time at -80 °C. Therefore, we performed g...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/s12865-016-0144-1

    authors: Yang J,Diaz N,Adelsberger J,Zhou X,Stevens R,Rupert A,Metcalf JA,Baseler M,Barbon C,Imamichi T,Lempicki R,Cosentino LM

    更新日期:2016-03-15 00:00:00

  • Prothymosin α and a prothymosin α-derived peptide enhance T(H)1-type immune responses against defined HER-2/neu epitopes.

    abstract:BACKGROUND:Active cancer immunotherapies are beginning to yield clinical benefit, especially those using peptide-pulsed dendritic cells (DCs). Different adjuvants, including Toll-like receptor (TLR) agonists, commonly co-administered to cancer patients as part of a DC-based vaccine, are being widely tested in the clini...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/1471-2172-14-43

    authors: Ioannou K,Derhovanessian E,Tsakiri E,Samara P,Kalbacher H,Voelter W,Trougakos IP,Pawelec G,Tsitsilonis OE

    更新日期:2013-09-22 00:00:00

  • Interleukin-1beta and tumour necrosis factor-alpha impede neutral lipid turnover in macrophage-derived foam cells.

    abstract:BACKGROUND:Pro-inflammatory cytokines can affect intracellular lipid metabolism. A variety of effects have been described for different cell types; hepatocyte lipid turnover pathways are inhibited during inflammation, whereas interleukin-1beta (IL-1beta) reduces intracellular cholesterol levels in fibroblasts. Levels o...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/1471-2172-9-70

    authors: Persson J,Nilsson J,Lindholm MW

    更新日期:2008-11-25 00:00:00

  • Low-dose plasmid DNA treatment increases plasma vasopressin and regulates blood pressure in experimental endotoxemia.

    abstract:BACKGROUND:Although plasmid DNA encoding an antigen from pathogens or tumor cells has been widely studied as vaccine, the use of plasmid vector (without insert) as therapeutic agent requires further investigation. RESULTS:Here, we showed that plasmid DNA (pcDNA3) at low doses inhibits the production of IL-6 and TNF-α ...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/1471-2172-13-59

    authors: Malardo T,Batalhão ME,Panunto-Castelo A,Almeida LP,Padilha E,Fontoura IC,Silva CL,Carnio EC,Coelho-Castelo AA

    更新日期:2012-11-08 00:00:00

  • Impaired T-cell proliferation among HAART-treated adults with suboptimal CD4 recovery in an African cohort.

    abstract:BACKGROUND:Most HIV-infected subjects exhibit a progressive rise in CD4 T-cell counts after initiation of highly active antiretroviral therapy (HAART). However, a subset of individuals exhibit very poor CD4 T-cell recovery despite effective control of HIV-RNA viraemia. We evaluated CD4 T-cell proliferation among subopt...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/1471-2172-14-26

    authors: Nakanjako D,Ssewanyana I,Nabatanzi R,Kiragga A,Kamya MR,Cao H,Mayanja-Kizza H

    更新日期:2013-06-20 00:00:00

  • Selection of reliable reference genes for the normalisation of gene expression levels following time course LPS stimulation of murine bone marrow derived macrophages.

    abstract:BACKGROUND:Macrophages are key players in the initiation, perpetuation and regulation of both innate and adaptive immune responses. They largely perform these roles through modulation of the expression of genes, especially those encoding cytokines. Murine bone marrow derived macrophages (BMDMs) are commonly used as a m...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/s12865-017-0223-y

    authors: Tanaka A,To J,O'Brien B,Donnelly S,Lund M

    更新日期:2017-10-03 00:00:00

  • Renal allograft rejection, lymphocyte infiltration, and de novo donor-specific antibodies in a novel model of non-adherence to immunosuppressive therapy.

    abstract:BACKGROUND:Non-adherence has been associated with reduced graft survival. The aim of this study was to investigate the immunological mechanisms underlying chronic renal allograft rejection using a model of non-adherence to immunosuppressive therapy. We used a MHC (major histocompatibility complex) -mismatched rat model...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/s12865-017-0236-6

    authors: Kühne L,Jung B,Poth H,Schuster A,Wurm S,Ruemmele P,Banas B,Bergler T

    更新日期:2017-12-19 00:00:00

  • Distinct roles for nitric oxide in resistant C57BL/6 and susceptible BALB/c mice to control Burkholderia pseudomallei infection.

    abstract:BACKGROUND:Burkholderia pseudomallei is the causative agent of melioidosis, an emerging bacterial infectious disease in tropical and subtropical areas. We recently showed that NADPH oxidase but not nitric oxide (NO) contributes to resistance in innately resistant C57BL/6 mice in a B. pseudomallei respiratory infection ...

    journal_title:BMC immunology

    pub_type: 杂志文章

    doi:10.1186/1471-2172-12-20

    authors: Breitbach K,Wongprompitak P,Steinmetz I

    更新日期:2011-03-16 00:00:00