Abstract:
:The signaling adapters MyD88 and TRIF are engaged by TLRs and/or receptors of the IL-1 family and are considered important for innate immune responses that combat bacterial infections. Here, the consequences of a combined MyD88 and TRIF deficiency for the innate immune response against severe septic peritonitis was examined. We demonstrate that Myd88(-/-);Trif(Lps2/Lps2) mice had markedly reduced bacterial numbers in the peritoneal cavity and peripheral blood, indicating that bacterial clearance in this model is improved in the absence of MyD88/TRIF signals. Survival of Myd88(-/-); Trif(Lps2/Lps2) mice was improved significantly. The lack of MyD88/TRIF signaling prevented the excessive production of inflammatory cytokines and of IL-10. In contrast, Ifng mRNA was expressed at WT levels, and induction of Ifnb mRNA was reduced only by one-half. Consistent with these findings, numerous IFN-regulated genes, including p47 and p65 GTPases, as well as CXCL10, were expressed in a MyD88/TRIF-independent manner. In support of the in vivo data, Myd88(-/-); Trif(Lps2/Lps2) macrophages stimulated with live intestinal bacteria produced normal amounts of CXCL10. The production of p47 GTPases and CXCL10 in septic peritonitis was found to be dependent on the presence of IFNAR1, but not IFN-γ, indicating a normal induction of the type I IFN response in Myd88(-/-);Trif(Lps2/Lps2) mice, despite attenuated IFN-β production. Together, these results provide evidence that in severe septic peritonitis, the absence of MyD88 and TRIF balances the innate immune response in a favorable manner by attenuating deleterious responses such as excessive cytokine release, while leaving intact protective IFN responses.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Reim D,Rossmann-Bloeck T,Jusek G,Prazeres da Costa O,Holzmann Bdoi
10.1189/jlb.1110602subject
Has Abstractpub_date
2011-09-01 00:00:00pages
613-20issue
3eissn
0741-5400issn
1938-3673pii
jlb.1110602journal_volume
90pub_type
杂志文章abstract::CD4(+) T cell help contributes critically to DC-induced CD8(+) CTL immunity. However, precisely how these three cell populations interact and how CD4(+) T cell signals are delivered to CD8(+) T cells in vivo have been unclear. In this study, we developed a novel, two-step approach, wherein CD4(+) T cells and antigen-p...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1211631
更新日期:2012-08-01 00:00:00
abstract::The ability of encapsulated and acapsular strains of Cryptococcus neoformans to activate dendritic cells (DC) derived from monocytes stimulated with granulocyte macrophage-colony stimulating factor and interleukin-4 was evaluated. Profound differences in DC response to encapsulated and acapsular C. neoformans strains ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1002476
更新日期:2003-09-01 00:00:00
abstract::We have sought to elucidate the responses of human peripheral blood neutrophils to antigenic surfaces complexed with human specific IgA antibodies obtained either as myeloma proteins that recognize staphylococcal alpha-toxin, or from the serum of patients with subacute bacterial endocarditis due to Streptococcus mutan...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.57.6.875
更新日期:1995-06-01 00:00:00
abstract::Bacterial and viral infections cause high rates of morbidity and mortality in premature newborns. In the setting of viral infection, pDCs play a key role as strong producers of IFN-α upon TLR9 activation. We analyzed pDC frequency, phenotype, morphology, and function in CB of preterm and term newborns in comparison wi...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1011525
更新日期:2013-05-01 00:00:00
abstract::Changes in leukocyte subpopulations and function after spaceflight have been observed but the mechanisms underlying these changes are not well defined. This study investigated the effects of short-term spaceflight (8-15 days) on circulating leukocyte subsets, stress hormones, immunoglobulin levels, and neutrophil func...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.65.2.179
更新日期:1999-02-01 00:00:00
abstract::The last 10-15 years have witnessed a revolution in treating multiple myeloma, an incurable cancer of Ab-producing plasma cells. Advances in myeloma therapy were ushered in by novel agents that remodel the myeloma immune microenvironment. The first generation of novel agents included immunomodulatory drugs (thalidomid...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/jlb.3MR1116-468R
更新日期:2017-08-01 00:00:00
abstract::Discussion on targeting LXR and PPAR agonists as therapeutic alternatives to ustekinumab therapy in LAD-1. ...
journal_title:Journal of leukocyte biology
pub_type: 社论
doi:10.1002/JLB.5CE0520-122R
更新日期:2020-11-01 00:00:00
abstract::The rapid and efficient expansion of CD8(+) memory T cells after the second encounter with a pathogen constitutes a hallmark trait of adaptive immunity. Yet, the contribution of CD4(+) T cells to the expansion of memory CD8(+) T cells remains the subject of controversy. Here, we show that, antigen-specific CD4(+) T ce...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0506321
更新日期:2006-12-01 00:00:00
abstract::The transmembrane form of tumor necrosis factor (mTNF), expressed on activated monocytes (MO) and macrophages (MPhi), is able to induce apoptosis in human endothelial cells (EC). Apoptosis is mediated by two distinct mechanisms: direct cell contact and a yet-unidentified soluble protein, death factor X. In addition, m...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0703343
更新日期:2004-02-01 00:00:00
abstract::Fluoroquinolones have immunomodulatory properties and interfere with cytokine production. The aim of this study was to characterize the extent of the superinduced mRNA levels in activated human lymphocytes incubated with ciprofloxacin (5 and 80 micro g/ml) using a cytokine gene expression microarray from R and D Syste...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0103048
更新日期:2003-09-01 00:00:00
abstract::The adhesion molecule CD44 consists of many isoforms of which particularly CD44v7 is of major importance in hematopoietic progenitor cell homing. An increase of progenitor cells in the periphery was observed after treating mice with a CD44v7-specific antibody, concomitant with a substantially augmented marrow-repopula...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2001-03-01 00:00:00
abstract::We investigated the hypothesis that transmigration drives monocyte transcriptional changes. Using Agilent whole human genome microarrays, we identified over 692 differentially expressed genes (2x, P<0.05) in freshly isolated human monocytes following 1.5 h of transmigration across IL-1beta-stimulated ECs compared with...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0209062
更新日期:2009-12-01 00:00:00
abstract::Glycoprotein 130 (gp130) is a shared receptor utilized by several related cytokines, including IL-6, IL-11, IL-27, Leukemia Inhibitory Factor (LIF), Oncostatin M (OSM), Ciliary Neurotrophic Factor (CNTF), Cardiotrophin 1 (CT-1) and Cardiotrophin-like Cytokine (CLC). Gp130 plays critical roles during development and gp...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/jlb.0410217
更新日期:2010-12-01 00:00:00
abstract::Monocyte chemoattractant protein-1 (MCP-1, CCL2) is a mediator of inflammation that has been implicated in the pathogenesis of a wide variety of human diseases. CCR2, a heterotrimeric G-coupled receptor, is the only known receptor that functions at physiologic concentrations of MCP-1. Despite the importance of CCR2 in...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0903421
更新日期:2004-06-01 00:00:00
abstract::Human activated T cells adhere to synovial fibroblast-like cells in vitro. The present study was conducted to investigate the consequences of T cell-synovial fibroblast interactions with regard to induction of adhesion molecules and proinflammatory cytokines. A sensitive Western blot technique, polymerase chain reacti...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.54.5.399
更新日期:1993-11-01 00:00:00
abstract::Exposure of lymphocytes from guinea pigs sensitized to keyhole limpet hemocyanin and of macrophages from nonsensitized animals to noncytotoxic doses of lidocaine (10(-4) to 10(-6) M) resulted in the inhibition of the production of macrophage migration inhibitory factor and of macrophage motility. The inhibition of bot...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.36.5.621
更新日期:1984-11-01 00:00:00
abstract::Neutrophils are quickly recruited to tissues in response to proinflammatory cues; however, little is known about tissue neutrophil phenotypes in health. We employ a multicolor flow cytometric approach to assess surface markers of activation on neutrophils from the bone marrow, blood, peritoneum, spleen, liver, fat, co...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/JLB.4AB1020-248RRR
更新日期:2020-11-04 00:00:00
abstract::The RAGE binds multiple ligand families linked to hyperglycemia, aging, inflammation, neurodegeneration, and cancer. Activation of RAGE by its ligands stimulates diverse signaling cascades. The recent observation that the cytoplasmic domain of RAGE interacts with diaphanous or mDia-1 links RAGE signal transduction to ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/jlb.0409230
更新日期:2009-09-01 00:00:00
abstract::In previous studies, macrophages have been shown to influence in vitro colony formation by erythroid progenitors (CFU-E). To determine whether the origin of the macrophages influences their effects on in vitro erythropoiesis, plasma clot cultures of CFU-E were grown over adherent monolayers of macrophages from various...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.36.5.581
更新日期:1984-11-01 00:00:00
abstract::This short review focuses on the role of central nervous system (CNS) perivascular macrophages as targets of productive infection of the CNS. Data discussed include the importance of these cells as early targets of infection and their productive infection with AIDS. Many of the immune molecules on perivascular macroph...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/jlb.0503207
更新日期:2003-11-01 00:00:00
abstract::Complement component C1q is a member of a family of soluble proteins called defense collagens, which are important in host defense and apoptotic cell clearance. Failure to efficiently clear apoptotic cells in the absence of C1q is associated with autoimmunity. Here, we review the literature describing a central role f...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/jlb.0212099
更新日期:2012-09-01 00:00:00
abstract::T cell-mediated immunity against Chlamydia in mice is mediated at least in part by T cell-derived interferon-gamma (IFN-gamma) induction of the nitric oxide synthase (iNOS) system in infected epithelial cells. Although IFN-gamma alone could stimulate nitric oxide (NO) production from epithelial cells and inhibit the i...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.59.5.656
更新日期:1996-05-01 00:00:00
abstract::The airway epithelial cell of the lower respiratory tract is the primary host target cell for respiratory syncytial virus (RSV) infection. To estimate whether infected epithelial cells contribute to the inflammatory host response observed during the acute infection phase we analyzed the cell surface expression of inte...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.60.6.766
更新日期:1996-12-01 00:00:00
abstract::The Fc gamma receptor IIB (FcγRIIB/CD32B) was generated million years ago during evolution. It is the sole inhibitory receptor for IgG, and has long been associated with the regulation of humoral immunity and innate immune homeostasis. However, new and surprising functions of FcγRIIB are emerging. In particular, FcγRI...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1002/JLB.2MIR0917-354R
更新日期:2018-02-06 00:00:00
abstract::The ellipsoid-associated cells (EAC) localize on the surface of the ellipsoid. They bind the IV injected horseradish peroxidase (HRP) and bovine serum albumin (BSA), migrate to the red pulp and then enter the systemic circulation. After protein injection, the number of white blood cells increased above the normal leve...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.35.5.501
更新日期:1984-05-01 00:00:00
abstract::In this study we describe the isolation and characterization of a new chicken (Gallus gallus) chemokine. This molecule belongs to the C or gamma-chemokine family and is related to the mouse and human lymphotactin (Lptn). Mouse and human Lptn are distinguished from alpha and beta chemokines by the absence of two cystei...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.65.1.87
更新日期:1999-01-01 00:00:00
abstract::Adherence of monocytes to extracellular matrix components is critical for their accumulation at sites of infection. To gain insight into the factors that regulate monocyte recruitment, we have studied monocyte adherence with regard to the regulatory effects of bacterial lipopolysaccharide (LPS) and the mechanisms invo...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.51.4.400
更新日期:1992-04-01 00:00:00
abstract::It has been shown that lead (Pb) potentiates lipopolysaccharide (LPS) lethality in animals by increasing the secretion and uptake or reactivity of tumor necrosis factor-alpha (TNF-alpha). Herein we report that PbCl2 increased TNF-alpha secretion from LPS-treated human peripheral blood mononuclear cells (PBMC) in a con...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.59.6.932
更新日期:1996-06-01 00:00:00
abstract::Viral recognition programs DCs to express Signal 3 molecules that promote the differentiation of effector CD8(+) T cells. Besides IL-12, another DC-derived IL-12 family member, IL-27, has been reported to contribute herein, but its specific role is not well understood. Here, we show that whereas IL-12 potently induces...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0112045
更新日期:2012-09-01 00:00:00
abstract::Macrophages in brain, lung, and lymphatics constitute a major HIV reservoir during subclinical infection and disease. During HIV transmission macrophages are seemingly one of the first cells infected, being as efficient as T cells in supporting productive viral replication. Macrophages control a myriad of cell-mediate...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1002/jlb.56.3.278
更新日期:1994-09-01 00:00:00