Abstract:
:Macrophage (MΦ) polarization is triggered during the innate immune response to defend against microbial pathogens, but can also contribute to disease pathogenesis. In a previous study, we found that interleukin-15 (IL-15) -derived classically activated macrophages (M1 MΦ) have enhanced antimicrobial activity, whereas IL-10-derived alternatively activated macrophages (M2 MΦ) were highly phagocytic but lacked antimicrobial activity. Given that the ability to modulate MΦ polarization from M2 MΦ to M1 MΦ may promote a more effective immune response to infection, we investigated the plasticity of these MΦ programs. Addition of IL-10 to M1 MΦ induced M2-like MΦ, but IL-15 had little effect on M2 MΦ. We determined the set of immune receptors that are present on M2 MΦ, elucidating two candidates for inducing plasticity of M2 MΦ, Toll-like receptor 1 (TLR1) and interferonγ (IFN-γ) receptor 1. Stimulation of M2 MΦ with TLR2/1 ligand (TLR2/1L) or IFN-γ alone was not sufficient to alter M2 MΦ phenotype or function. However, co-addition of TLR2/1L and IFN-γ re-educated M2 MΦ towards the M1 MΦ phenotype, with a decrease in the phagocytosis of lipids and mycobacteria, as well as recovery of the vitamin-D-dependent antimicrobial pathway compared with M2 MΦ maintained in polarizing conditions. Similarly, treatment of M2 MΦ with both TLR2/1L and anti-IL-10 neutralizing antibodies led to polarization to the M1-like MΦ phenotype and function. Together, our data demonstrate an approach to induce MΦ plasticity that provides the potential for re-educating MΦ function in human mycobacterial disease to promote host defense and limit pathogenesis.
journal_name
Immunologyjournal_title
Immunologyauthors
Montoya D,Mehta M,Ferguson BG,Teles RMB,Krutzik SR,Cruz D,Pellegrini M,Modlin RLdoi
10.1111/imm.13013subject
Has Abstractpub_date
2019-02-01 00:00:00pages
164-173issue
2eissn
0019-2805issn
1365-2567journal_volume
156pub_type
杂志文章相关文献
IMMUNOLOGY文献大全abstract::Treatment of b4b6 rabbit peripheral blood lymphocytes with b5b5 anti-b4 antibodies at 4 degrees resulted in the modulation (disappearance) ob b4 and b6 cell surface allotype after subsequent incubation in serum-free medium for 1 h at 37 degrees. A clear dose dependence on the sensitizing anti-b4 antibody was observed....
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1978-04-01 00:00:00
abstract::Mesangial hypercellularity is usually found in many models of nephritis characterized by monocyte/macrophage infiltration of the glomerulus. In order to examine the mechanism mediating these events, an in vitro model was used to study the effects of macrophage products on mouse mesangial cells, cultured under conditio...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1985-12-01 00:00:00
abstract::Members of the tumour necrosis factor receptor superfamily play a key role in B-lymphocyte survival, proliferation, differentiation and programmed cell death. A member of this superfamily, the CD40 molecule plays an important role in the differentiation of B lymphocytes into effector cells and in early activation thro...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1046/j.1365-2567.1997.00159.x
更新日期:1997-02-01 00:00:00
abstract::Mice of the strains A.TH and A.TL were rendered neonatally tolerant to class II major histocompatibility complex (MHC) by the injection of (A.TH x A.TL)F1 spleen and bone marrow cells within 24 hr of birth. Spleen and thymus cells from adult tolerant mice bearing long-term surviving skin grafts were compared with thos...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1993-08-01 00:00:00
abstract::Although the co-stimulatory interaction between B and T cells is well defined, recent evidence suggests that B cells also have a regulatory role. Here, we show that B cells activated using anti-IgD conjugated to dextran (α-δ-dex) directly inhibit TCR-induced CD4 T cell activation, proliferation and cytokine production...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/imm.12389
更新日期:2014-09-20 00:00:00
abstract::Mice injected with rat erythrocytes developed anti-erythrocyte autoantibodies which reached a plateau at 4-12 weeks, then gradually declined until at about 24 weeks the majority of mice were negative. In such recovered mice re-challenge with rat erythrocytes produced an accelerated peak of autoantibody and a much more...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1980-04-01 00:00:00
abstract::We have recently described a bone marrow culture system which is able to maintain a portion of the precursor-T (pre-T) cell compartment of adult murine marrow in vitro, in the presence of interleukin-3 (IL-3), for at least 2 weeks. However, because growth in IL-3 might also induce the differentiation of the pre-T cell...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1992-06-01 00:00:00
abstract::T cells from mice injected with picryl sulphonic acid (PSA) inhibit the expression of contact sensitivity to picryl chloride. Adult thymectomy (aTx) prevents the production of cells which inhibit the effector stage but cells from aTx mice are, however, still able to suppress the induction of contact sensitivity. These...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1981-01-01 00:00:00
abstract::The molecular characteristics of a serum IL-2 inhibitor were determined by fractionating active sera from normal and malaria-infected mice, and assaying inhibitory activity in blocking production and expression of IL-2 activity. Using isoelectric focusing and ion exchange chromatography, the activity resolved in a sin...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1985-09-01 00:00:00
abstract::Haptoglobin (Hp), a major acute-phase plasma protein, has been found in arthritic synovial fluid (SF). However, the function and structural modifications of Hp in arthritic SF are unknown. To investigate in vivo generation of modified Hp associated with inflammatory disease, we examined a new Hp isoform in SF from pat...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/imm.12125
更新日期:2013-09-01 00:00:00
abstract::Membrane sialoglycoprotein (GP) of mouse erythrocytes were incorporated into artificial membranes of liposomes which also contained DNP-aminocaproylphosphatidylethanolamine hapten. The liposomes were tested for their potential to modulate the anti-hapten antibody response in mice as a plausible model of haptenated iso...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1984-12-01 00:00:00
abstract::In this study, we describe the ability of hybrid mouse monoclonal antibody (mAb) to induce monocyte-mediated cytotoxicity towards human IgA1-coated E (HuIgA1-E), and the effect of mAb binding valency on Fc gamma RI-mediated ADCC. All hybrid monospecific (ms) anti-HuIgA1 and bispecific (bs) anti-HuIgA1/HRP mAb were cap...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1992-02-01 00:00:00
abstract::We and others have established an important role for phosphoinositide-3 kinase gamma (PI3Kgamma) in the chemotactic responses of macrophages and neutrophils. The involvement of this lipid kinase in allergic inflammatory responses is, however, yet to be fully determined. Here we compare wild-type (WT) and PI3Kgamma(-/-...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2567.2008.02908.x
更新日期:2009-03-01 00:00:00
abstract::Class switch recombination (CSR) is a T-cell-dependent mechanism regulating isotype switching in activated mature B cells. Recently we showed that T-cell-independent CSRs occur spontaneously during B lymphopoiesis, but such cells are negatively selected by Fas signalling. In immunoglobulin mu-deficient mice, lack of F...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2567.2004.01883.x
更新日期:2004-06-01 00:00:00
abstract::Previous studies have highlighted the importance of CD4+ T cells in regulation of IgA responses and have indicated a functional heterogeneity among these cells between inductive (Peyer's patch) and effector (lamina propria) sites in the intestine. To determine whether these functional differences could be accounted fo...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1993-12-01 00:00:00
abstract::Different cell types, including dendritic cells, macrophages and Ia+ B cells, have been described to present soluble antigen (Ag) to T-cell hybridomas. However, it is still not clear whether these different cell types can act as antigen-presenting cells (APC) for complex and insoluble Ag such as viral particles. Using...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1991-05-01 00:00:00
abstract::While many aspects of memory T-cell immunobiology have been characterized, we suggest that we know only a fraction of the effector functions that CD4 T cells can bring to bear during secondary challenges. Exploring the full impact of memory CD4 T-cell responses is key to the development of improved vaccines against ma...
journal_title:Immunology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2567.2010.03259.x
更新日期:2010-05-01 00:00:00
abstract::The fate of allogeneic lymphocytes (AO or DA) transferred to non-immune PVG recipients was studied in the light of previous evidence (Heslop & McNeilage, 1983; Rolstad & Ford, 1983) that allogeneic lymphocytes can be rapidly destroyed in certain strain combinations of rats and mice by a mechanism that is distinct from...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract::A critical role for leukotriene B(4) (LTB(4)) and/or platelet-activating factor (PAF) in regulating polymorphonuclear cell (PMN) trafficking to inflammatory sites has been reported in a number of experimental inflammatory models. In vitro, newly synthesized LTB(4) and PAF were shown to act in an autocrine/paracrine or...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2567.2007.02767.x
更新日期:2008-07-01 00:00:00
abstract::Mercuric chloride (HgCl2)-induced autoimmunity in Brown Norway rats is a spontaneously resolving autoimmune response driven by the activation of T helper type 2 lymphocytes (Th2 cells). Treatment with antibody to OX40-ligand (OX40-L) from the time of the first HgCl2 injection for 12 days had little effect. Delayed tre...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2567.2005.02314.x
更新日期:2006-03-01 00:00:00
abstract::Variation in the sequence of T-cell epitopes between dengue virus (DENV) serotypes is believed to alter memory T-cell responses during second heterologous infections. We identified a highly conserved, novel, HLA-B57-restricted epitope on the DENV NS1 protein. We predicted higher frequencies of B57-NS1(26-34) -specific...
journal_title:Immunology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1111/imm.12161
更新日期:2014-01-01 00:00:00
abstract::Despite extensive investigation of the signals required for development of T helper type 1 (Th1) and type 2 (Th2) immune responses, the mechanisms involved are still not well-defined. A critical role for Epstein-Barr virus-induced gene 3 (EBI3) in these responses has been proposed. EBI3, initially discovered as a tran...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2567.2010.03401.x
更新日期:2011-04-01 00:00:00
abstract::Synthesis of interferon (IFN)-gamma by natural killer (NK) cells is an important pro-inflammatory event with interleukin (IL)-12 and IL-18 playing major inductive roles. However, other temporal events are likely to regulate such processes and as prostaglandin E2 (PGE2) is ubiquitous during inflammation this study test...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2567.2004.01810.x
更新日期:2004-03-01 00:00:00
abstract::Although it is well known that cases with silicosis exhibit various immunological abnormalities, the mechanisms involved in the occurrence of immuno-dysfunction or dysregulation induced by silica compounds have not yet been determined. Fas is a well-known cell surface molecule that is involved in the apoptosis pathway...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1046/j.1365-2567.1998.00509.x
更新日期:1998-06-01 00:00:00
abstract::The influence of antigens of the major histocompatibility complex (MHC) on the production of interferon (IFN) alpha or IFN gamma by human peripheral blood leucocytes (PBL) in vitro has been studied. Synthesis of IFN gamma by PBL stimulated with purified phytohaemagglutinin (PHA-P) or protein A of Staphylococcus aureus...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1983-06-01 00:00:00
abstract::Urokinase-type plasminogen activator (u-PA), tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) activities were measured for highly purified human monocytes cultured for 18 hr with recombinant human interleukin-3 (IL-3). IL-3 alone stimulated monocyte u-PA activity, but not TNF-alpha or IL-1 activity. H...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1990-09-01 00:00:00
abstract::We have studied the antibody response in vitro of spleen cells from C57BL/6 mice kept on a protein deficient (D) or a normal diet (N). Short or long term protein restriction initiated after weaning led to increased plaque forming cell (PFC) responses to sheep red blood cells (SRBC), TNP-ficoll and TNP lipopolysacchari...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1981-06-01 00:00:00
abstract::Histamine not only mediates immediate allergic reactions, it also regulates cellular immune responses. H4R is the most recently identified histamine receptor (HR). In the present study, we examined the in vitro effect of histamine and H4R agonists on the responses of human T cells to purified protein derivative from M...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2567.2007.02574.x
更新日期:2007-06-01 00:00:00
abstract::Invariant natural killer T (iNKT) cells are an innate population of T cells identified by the expression of an invariant T-cell receptor and reactivity to lipid-based antigens complexed with CD1d. They account for a small percentage of lymphocytes, but are extremely potent and play central roles in immunity to infecti...
journal_title:Immunology
pub_type: 杂志文章,评审
doi:10.1111/imm.12481
更新日期:2015-08-01 00:00:00
abstract::Systemic lupus erythematosus (SLE) is an autoimmune disease in which abnormal immune responses are mediated by tissue-binding autoantibodies and immune complex deposition. Because most SLE patients are women of child-bearing age, oestrogen has been suggested to play an important role in SLE pathogenesis. One proposed ...
journal_title:Immunology
pub_type: 临床试验,杂志文章
doi:10.1111/imm.12263
更新日期:2014-08-01 00:00:00